{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:48:22Z","timestamp":1791298102433,"version":"4.1.0"},"reference-count":128,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2015,3,6]],"date-time":"2015-03-06T00:00:00Z","timestamp":1425600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Mutations in the X-linked gene MECP2, the founding member of a family of proteins recognizing and binding to methylated DNA, are the genetic cause of a devastating neurodevelopmental disorder in humans, called Rett syndrome. Available evidence suggests that MECP2 protein has a critical role in activity-dependent neuronal plasticity and transcription during brain development. Moreover, recent studies in mice show that various posttranslational modifications, notably phosphorylation, regulate Mecp2\u2019s functions in learning and memory, drug addiction, depression-like behavior, and the response to antidepressant treatment. The hypothalamic-pituitary-adrenal (HPA) axis drives the stress response and its deregulation increases the risk for a variety of mental disorders. Early-life stress (ELS) typically results in sustained HPA-axis deregulation and is a major risk factor for stress related diseases, in particular major depression. Interestingly, Mecp2 protein has been shown to contribute to ELS-dependent epigenetic programming of Crh, Avp, and Pomc, all of these genes enhance HPA-axis activity. Hereby ELS regulates Mecp2 phosphorylation, DNA binding, and transcriptional activities in a tissue-specific and temporospatial manner. Overall, these findings suggest MECP2 proteins are so far underestimated and have a more dynamic role in the mediation of the gene-environment dialog and epigenetic programming of the neuroendocrine stress system in health and disease.<\/jats:p>","DOI":"10.3390\/genes6010060","type":"journal-article","created":{"date-parts":[[2015,3,6]],"date-time":"2015-03-06T10:38:33Z","timestamp":1425638313000},"page":"60-86","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Role of Mecp2 in Experience-Dependent Epigenetic Programming"],"prefix":"10.3390","volume":"6","author":[{"given":"Christoph","family":"Zimmermann","sequence":"first","affiliation":[{"name":"Max Planck Institute of Psychiatry, Translational Research, Kraepelinstr. 2-10,  Munich 80804, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anke","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Max Planck Institute of Psychiatry, Translational Research, Kraepelinstr. 2-10,  Munich 80804, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Raabe","sequence":"additional","affiliation":[{"name":"Max Planck Institute of Psychiatry, Translational Research, Kraepelinstr. 2-10,  Munich 80804, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dietmar","family":"Spengler","sequence":"additional","affiliation":[{"name":"Max Planck Institute of Psychiatry, Translational Research, Kraepelinstr. 2-10,  Munich 80804, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,3,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Waddington, C.H. (2014). The Strategy of the Genes. A Discussion of Some Aspects of Theoretical Biology, Routledge.","DOI":"10.4324\/9781315765471"},{"key":"ref_2","unstructured":"Russo, V.E.A., Martienssen, R.A., and Riggs, A.D. (1996). Epigenetic Mechanisms of Gene Regulation, Cold Spring Harbor Laboratory Press."},{"key":"ref_3","unstructured":"Allis, C.D., Jenuwein, T., and Reinberg, D. (2007). Epigenetics, Cold Spring Harbor Laboratory Press."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.molmed.2014.03.004","article-title":"MeCP2: The long trip from a chromatin protein to neurological disorders","volume":"20","author":"Esteller","year":"2014","journal-title":"Trends Mol. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.neuron.2007.10.001","article-title":"The story of rett syndrome: From clinic to neurobiology","volume":"56","author":"Chahrour","year":"2007","journal-title":"Neuron"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1007\/s11920-012-0255-1","article-title":"Genetic variation in the epigenetic machinery and mental health","volume":"14","author":"Murgatroyd","year":"2012","journal-title":"Curr. Psychiatry Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1101\/gad.947102","article-title":"DNA methylation patterns and epigenetic memory","volume":"16","author":"Bird","year":"2002","journal-title":"Genes Dev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1146\/annurev.psych.60.110707.163625","article-title":"Epigenetics and the environmental regulation of the genome and its function","volume":"61","author":"Zhang","year":"2010","journal-title":"Annu. Rev. Psychol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"194","DOI":"10.4161\/epi.5.3.11375","article-title":"Genes learn from stress: How infantile trauma programs us for depression","volume":"5","author":"Murgatroyd","year":"2010","journal-title":"Epigenetics"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.neuroscience.2012.04.003","article-title":"DNA memories of early social life","volume":"264","author":"Hoffmann","year":"2014","journal-title":"Neuroscience"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.cell.2007.02.006","article-title":"Epigenetics: A landscape takes shape","volume":"128","author":"Goldberg","year":"2007","journal-title":"Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1038\/447395a","article-title":"Insight: Introduction Epigenetics","volume":"447","author":"Eccleston","year":"2007","journal-title":"Nature"},{"key":"ref_13","unstructured":"Tollefsbol, T.O. (2010). Handbook of Epigenetics: The New Molecular and Medical Genetics, Academic Press. [1 edition]."},{"key":"ref_14","unstructured":"Armstrong, L. (2013). Epigenetics, Garland Science."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Lister, R., Mukamel, E.A., Nery, J.R., Urich, M., Puddifoot, C.A., Johnson, N.D., Lucero, J., Huang, Y., Dwork, A.J., and Schultz, M.D. (2013). Global epigenomic reconfiguration during mammalian brain development. Science, 341.","DOI":"10.1126\/science.1237905"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2787","DOI":"10.1242\/jcs.015123","article-title":"Mammalian cytosine methylation at a glance","volume":"122","author":"Ooi","year":"2009","journal-title":"J. Cell Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"25893","DOI":"10.1074\/jbc.M603140200","article-title":"Reconstitution and mechanism of the stimulation of de Novo methylation by human DNMT3L","volume":"281","author":"Kareta","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1073\/pnas.0510310103","article-title":"A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two distinct classes of promoters","volume":"103","author":"Saxonov","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/hdy.2010.54","article-title":"Epigenetics and gene expression","volume":"105","author":"Gibney","year":"2010","journal-title":"Heredity"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"R10","DOI":"10.1186\/gb-2011-12-1-r10","article-title":"DNA methylation patterns associate with genetic and gene expression variation in HapMap cell lines","volume":"12","author":"Bell","year":"2011","journal-title":"Genome Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/nature11232","article-title":"The accessible chromatin landscape of the human genome","volume":"489","author":"Thurman","year":"2012","journal-title":"Nature"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/ng1990","article-title":"Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome","volume":"39","author":"Weber","year":"2007","journal-title":"Nat. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1126\/science.1186366","article-title":"Genome-Wide Evolutionary Analysis of Eukaryotic DNA Methylation","volume":"328","author":"Zemach","year":"2010","journal-title":"Science"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"8689","DOI":"10.1073\/pnas.1002720107","article-title":"Conservation and divergence of methylation patterning in plants and animals","volume":"107","author":"Feng","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/nature09165","article-title":"Conserved role of intragenic DNA methylation in regulating alternative promoters","volume":"466","author":"Maunakea","year":"2010","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e1000952","DOI":"10.1371\/journal.pgen.1000952","article-title":"Abundant quantitative trait loci exist for DNA methylation and gene expression in human brain","volume":"6","author":"Gibbs","year":"2010","journal-title":"PLoS Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e00523","DOI":"10.7554\/eLife.00523","article-title":"Passive and active DNA methylation and the interplay with genetic variation in gene regulation","volume":"2","author":"Lappalainen","year":"2013","journal-title":"eLife"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.cell.2013.12.019","article-title":"Reversing DNA methylation: Mechanisms, genomics, and Biological functions","volume":"156","author":"Wu","year":"2014","journal-title":"Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1126\/science.1170116","article-title":"Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1","volume":"324","author":"Tahiliani","year":"2009","journal-title":"Science"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1038\/nature09303","article-title":"Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification","volume":"466","author":"Ito","year":"2010","journal-title":"Nature"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1126\/science.1210597","article-title":"Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine","volume":"333","author":"Ito","year":"2011","journal-title":"Science"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1126\/science.1210944","article-title":"Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA","volume":"333","author":"He","year":"2011","journal-title":"Science"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.cell.2011.06.020","article-title":"Thymine DNA glycosylase is essential for active DNA demethylation by linked deamination-base excision repair","volume":"146","author":"Cortellino","year":"2011","journal-title":"Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2662","DOI":"10.4161\/cc.10.16.17093","article-title":"Emerging roles of TET proteins and 5-hydroxymethylcytosines in active DNA demethylation and beyond","volume":"10","author":"Guo","year":"2011","journal-title":"Cell Cycle"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"35334","DOI":"10.1074\/jbc.C111.284620","article-title":"Thymine DNA Glycosylase Can Rapidly Excise 5-formylcytosine and 5-carboxylcytosine potential implications for active demethylation of CpG sites","volume":"286","author":"Maiti","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1016\/j.cell.2013.02.004","article-title":"Dynamic readers for 5-(hydroxy)methylcytosine and its oxidized derivatives","volume":"152","author":"Spruijt","year":"2013","journal-title":"Cell"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.cell.2007.01.015","article-title":"The role of chromatin during transcription","volume":"128","author":"Li","year":"2007","journal-title":"Cell"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1016\/j.cell.2007.01.028","article-title":"Beyond the sequence: Cellular organization of genome function","volume":"128","author":"Misteli","year":"2007","journal-title":"Cell"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1038\/nsmb1333","article-title":"Chromatin remodeling: Insights and intrigue from single-molecule studies","volume":"14","author":"Cairns","year":"2007","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/nature05915","article-title":"The complex language of chromatin regulation during transcription","volume":"447","author":"Berger","year":"2007","journal-title":"Nature"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.cell.2007.01.033","article-title":"The mammalian epigenome","volume":"128","author":"Bernstein","year":"2007","journal-title":"Cell"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"6538","DOI":"10.1128\/MCB.18.11.6538","article-title":"Identification and characterization of a family of mammalian Methyl-CpG binding proteins","volume":"18","author":"Hendrich","year":"1998","journal-title":"Mol. Cell. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"12560","DOI":"10.1073\/pnas.0506071102","article-title":"Reduced cortical activity due to a shift in the balance between excitation and inhibition in a mouse model of Rett Syndrome","volume":"102","author":"Dani","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.neuron.2007.08.018","article-title":"MeCP2 controls excitatory synaptic strength by regulating glutamatergic synapse number","volume":"56","author":"Chao","year":"2007","journal-title":"Neuron"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.1073\/pnas.0812394106","article-title":"Partial reversal of Rett Syndrome-like symptoms in MeCP2 mutant mice","volume":"106","author":"Tropea","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1139\/O10-112","article-title":"MeCP2: structure and function","volume":"89","author":"Adkins","year":"2010","journal-title":"Biochem. Cell. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.ygeno.2004.12.002","article-title":"Distinct expression profiles of Mecp2 transcripts with different lengths of 3'UTR in the brain and visceral organs during mouse development","volume":"85","author":"Pelka","year":"2005","journal-title":"Genomics"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1093\/hmg\/11.2.115","article-title":"Insight into Rett syndrome: MeCP2 levels display tissue- and cell-specific differences and correlate with neuronal maturation","volume":"11","author":"Shahbazian","year":"2002","journal-title":"Hum. Mol. Genet."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.yhbeh.2010.05.014","article-title":"The role of MeCP2 in CNS development and function","volume":"59","author":"Na","year":"2011","journal-title":"Horm. Behav."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.molcel.2007.12.028","article-title":"MeCP2 binding to DNA depends upon hydration at methyl-CpG","volume":"29","author":"Ho","year":"2008","journal-title":"Mol. Cell"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.molcel.2005.07.021","article-title":"DNA binding selectivity of MeCP2 due to a requirement for A\/T sequences adjacent to methyl-CpG","volume":"19","author":"Klose","year":"2005","journal-title":"Mol. Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/561","article-title":"Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription","volume":"19","author":"Jones","year":"1998","journal-title":"Nat. Genet."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/S0092-8674(00)81887-5","article-title":"MeCP2 is a transcriptional repressor with abundant binding sites in genomic chromatin","volume":"88","author":"Nan","year":"1997","journal-title":"Cell"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1128\/MCB.01593-06","article-title":"Multiple modes of interaction between the methylated DNA binding protein MeCP2 and chromatin","volume":"27","author":"Nikitina","year":"2007","journal-title":"Mol. Cell. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2709","DOI":"10.1073\/pnas.0608056104","article-title":"Interaction between chromatin proteins MECP2 and ATRX is disrupted by mutations that cause inherited mental retardation","volume":"104","author":"Nan","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"4806","DOI":"10.1074\/jbc.M209923200","article-title":"Methyl-CpG-binding protein, MeCP2, is a target molecule for maintenance DNA methyltransferase, Dnmt1","volume":"278","author":"Kimura","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"4035","DOI":"10.1074\/jbc.M210256200","article-title":"The Methyl-CpG-binding protein MeCP2 links DNA methylation to histone methylation","volume":"278","author":"Fuks","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"34115","DOI":"10.1074\/jbc.M105747200","article-title":"The ski protein family is required for MeCP2-mediated transcriptional repression","volume":"276","author":"Kokura","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"49479","DOI":"10.1074\/jbc.M409070200","article-title":"Components of the DNA methylation system of chromatin control are RNA-binding proteins","volume":"279","author":"Jeffery","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.molcel.2010.01.030","article-title":"Neuronal MeCP2 is expressed at near histone-octamer levels and globally alters the chromatin state","volume":"37","author":"Skene","year":"2010","journal-title":"Mol. Cell"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"32181","DOI":"10.1074\/jbc.M305308200","article-title":"Chromatin compaction by human MeCP2 assembly of novel secondary chromatin structures in the absence of DNA methylation","volume":"278","author":"Georgel","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"19416","DOI":"10.1073\/pnas.0707442104","article-title":"Integrated epigenomic analyses of neuronal MeCP2 reveal a role for long-range interaction with active genes","volume":"104","author":"Yasui","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1523\/JNEUROSCI.4675-09.2010","article-title":"Alleviating transcriptional inhibition of the norepinephrine Slc6a2 transporter gene in depolarized neurons","volume":"30","author":"Harikrishnan","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.devcel.2009.12.017","article-title":"ATRX Partners with cohesin and MeCP2 and contributes to developmental silencing of imprinted genes in the brain","volume":"18","author":"Kernohan","year":"2010","journal-title":"Dev. Cell"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"15536","DOI":"10.1073\/pnas.242566899","article-title":"Transcriptional profiling of a mouse model for Rett syndrome reveals subtle transcriptional changes in the brain","volume":"99","author":"Tudor","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1146\/annurev-cellbio-092910-154121","article-title":"The role of MeCP2 in the brain","volume":"27","author":"Guy","year":"2011","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e415825","DOI":"10.1155\/2012\/415825","article-title":"Linking epigenetics to human disease and Rett syndrome: The emerging novel and challenging concepts in MeCP2 research","volume":"2012","author":"Zachariah","year":"2012","journal-title":"Neural Plast."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1126\/science.1153252","article-title":"MeCP2, a key contributor to neurological disease, activates and represses transcription","volume":"320","author":"Chahrour","year":"2008","journal-title":"Science"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2431","DOI":"10.1093\/hmg\/ddp181","article-title":"Mouse models of MeCP2 disorders share gene expression changes in the cerebellum and hypothalamus","volume":"18","author":"Chahrour","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2210","DOI":"10.1093\/hmg\/ddl146","article-title":"Ube3a expression is not altered in Mecp2 mutant mice","volume":"15","author":"Jordan","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"5033","DOI":"10.1128\/MCB.01665-05","article-title":"Gene expression analysis exposes mitochondrial abnormalities in a mouse model of rett syndrome","volume":"26","author":"Kriaucionis","year":"2006","journal-title":"Mol. Cell. Biol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.1093\/hmg\/ddi229","article-title":"Up-regulation of glucocorticoid-regulated genes in a mouse model of Rett syndrome","volume":"14","author":"Nuber","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3349","DOI":"10.1113\/jphysiol.2010.190926","article-title":"Significance of SGK1 in the regulation of neuronal function","volume":"588","author":"Lang","year":"2010","journal-title":"J. Physiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.tem.2011.08.001","article-title":"FKBP51 and FKBP52 in signaling and disease","volume":"22","author":"Storer","year":"2011","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"581","DOI":"10.3109\/10253890.2011.602146","article-title":"Epigenetic programming of the HPA axis: Early life decides","volume":"14","author":"Murgatroyd","year":"2011","journal-title":"Stress"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1210\/en.2013-1868","article-title":"Early-life stress reduces DNA methylation of the Pomc gene in male mice","volume":"155","author":"Wu","year":"2014","journal-title":"Endocrinology"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"18267","DOI":"10.1073\/pnas.0608702103","article-title":"Enhanced anxiety and stress-induced corticosterone release are associated with increased Crh expression in a mouse model of Rett syndrome","volume":"103","author":"McGill","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000076041","article-title":"Hypothalamic-pituitary-adrenocortical system and mood disorders: Highlights from mutant mice","volume":"79","author":"Uhr","year":"2004","journal-title":"Neuroendocrinology"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.neuron.2006.09.037","article-title":"Brain-specific phosphorylation of MeCP2 regulates activity-dependent Bdnf transcription, dendritic growth, and spine maturation","volume":"52","author":"Zhou","year":"2006","journal-title":"Neuron"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1038\/ng.1066","article-title":"Crh and Oprm1 mediate anxiety-related behavior and social approach in a mouse model of MECP2 duplication syndrome","volume":"44","author":"Samaco","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1002\/ana.21715","article-title":"Autism and other neuropsychiatric symptoms are prevalent in individuals with MeCP2 duplication syndrome","volume":"66","author":"Ramocki","year":"2009","journal-title":"Ann. Neurol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/j.neuropharm.2013.03.024","article-title":"BDNF deregulation in Rett syndrome","volume":"76","author":"Li","year":"2014","journal-title":"Neuropharmacology"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Bellini, E., Pavesi, G., Barbiero, I., Bergo, A., Chandola, C., Nawaz, M.S., Rusconi, L., Stefanelli, G., Strollo, M., and Valente, M.M. (2014). MeCP2 post-translational modifications: A mechanism to control its involvement in synaptic plasticity and homeostasis?. Front. Cell. Neurosci., 8.","DOI":"10.3389\/fncel.2014.00236"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1007\/s11515-014-1330-2","article-title":"Regulation and function of stimulus-induced phosphorylation of MeCP2","volume":"9","author":"Li","year":"2014","journal-title":"Front. Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1126\/science.1090842","article-title":"DNA methylation-related chromatin remodeling in activity-dependent Bdnf gene regulation","volume":"302","author":"Martinowich","year":"2003","journal-title":"Science"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1126\/science.1086446","article-title":"Derepression of BDNF transcription involves calcium-dependent phosphorylation of MeCP2","volume":"302","author":"Chen","year":"2003","journal-title":"Science"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"4882","DOI":"10.1073\/pnas.0811648106","article-title":"Phosphorylation of MeCP2 at Serine 80 regulates its chromatin association and neurological function","volume":"106","author":"Tao","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1038\/embor.2009.217","article-title":"Methyl\u2010CpG\u2010binding protein 2 is phosphorylated by homeodomain\u2010interacting protein kinase 2 and contributes to apoptosis","volume":"10","author":"Bracaglia","year":"2009","journal-title":"EMBO Rep."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2894","DOI":"10.1128\/MCB.06728-11","article-title":"Phosphorylation of distinct sites in MeCP2 modifies cofactor associations and the dynamics of transcriptional regulation","volume":"32","author":"Gonzales","year":"2012","journal-title":"Mol. Cell. Biol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.neuron.2011.08.022","article-title":"Genome-wide activity-dependent MeCP2 phosphorylation regulates nervous system development and function","volume":"72","author":"Cohen","year":"2011","journal-title":"Neuron"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1038\/nn.2866","article-title":"Loss of activity-induced phosphorylation of MeCP2 enhances synaptogenesis, LTP and spatial memory","volume":"14","author":"Li","year":"2011","journal-title":"Nat. Neurosci."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/35053570","article-title":"Molecular basis of long-term plasticity underlying addiction","volume":"2","author":"Nestler","year":"2001","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1146\/annurev.neuro.29.051605.113009","article-title":"Neural mechanisms of addiction: The role of reward-related learning and memory","volume":"29","author":"Hyman","year":"2006","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1124\/mol.106.022301","article-title":"Fluoxetine and cocaine induce the epigenetic factors MeCP2 and MBD1 in adult rat brain","volume":"70","author":"Cassel","year":"2006","journal-title":"Mol. Pharmacol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1038\/nn.2614","article-title":"MeCP2 in the nucleus accumbens contributes to neural and behavioral responses to psychostimulants","volume":"13","author":"Deng","year":"2010","journal-title":"Nat. Neurosci."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.neuint.2011.04.013","article-title":"Cocaine increases phosphorylation of MeCP2 in the rat striatum in vivo: A differential role of NMDA receptors","volume":"59","author":"Mao","year":"2011","journal-title":"Neurochem. Int."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"4519","DOI":"10.1523\/JNEUROSCI.2821-13.2014","article-title":"MeCP2 phosphorylation limits psychostimulant-induced behavioral and neuronal plasticity","volume":"34","author":"Deng","year":"2014","journal-title":"J. Neurosci."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/npp.2011.190","article-title":"Differential regulation of MeCP2 phosphorylation in the CNS by dopamine and serotonin","volume":"37","author":"Hutchinson","year":"2012","journal-title":"Neuropsychopharmacology"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.tins.2011.11.009","article-title":"Mood-stabilizing drugs: Mechanisms of action","volume":"35","author":"Schloesser","year":"2012","journal-title":"Trends Neurosci."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/nrn2866","article-title":"The habenula: from stress evasion to value-based decision-making","volume":"11","author":"Hikosaka","year":"2010","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1001\/archgenpsychiatry.2009.186","article-title":"Childhood adversities and adult psychiatric disorders in the national comorbidity survey replication i: Associations with first onset of DSM-IV disorders","volume":"67","author":"Green","year":"2010","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_102","unstructured":"U.S. Department of Health and Human Services; Administration for Children and Families; Administration on Children, Youth and Families. Children\u2019s Bureau Child. Maltreatment 2009, Available online:http:\/\/www.acf.hhs.gov\/programs\/cb\/stats_research\/index.htm#can."},{"key":"ref_103","unstructured":"U.S. Department of Health and Human Services; Administration for Children and Families; Administration on Children, Youth and Families; Children\u2019s Bureau Child. Maltreatment 2010, Available online:http:\/\/www.acf.hhs.gov\/programs\/cb\/stats_research\/index.htm#can."},{"key":"ref_104","unstructured":"American Professional Society on the Abuse of Children (1996). The APSAC Handbook on Child Maltreatment, SAGE Publications."},{"key":"ref_105","unstructured":"Institute of Medicine (U.S.), and National Research Council (U.S.) (2012). From Neurons to Neighborhoods: An Update: Workshop Summary, National Academies Press."},{"key":"ref_106","unstructured":"National Research Council (U.S.), Institute of Medicine (U.S.) (2009). Depression in Parents, Parenting, and Children: Opportunities to Improve Identification, Treatment, and Prevention, National Academies Press."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1176\/appi.ajp.160.8.1453","article-title":"Relationship between multiple forms of childhood maltreatment and adult mental health in community respondents: results from the adverse childhood experiences study","volume":"160","author":"Edwards","year":"2003","journal-title":"Am. J. Psychiatry"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/S0749-3797(98)00017-8","article-title":"Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults: The adverse childhood experiences (ACE) study","volume":"14","author":"Felitti","year":"1998","journal-title":"Am. J. Prev. Med."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.jad.2003.12.013","article-title":"Adverse childhood experiences and the risk of depressive disorders in adulthood","volume":"82","author":"Chapman","year":"2004","journal-title":"J. Affect. Disord."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"3089","DOI":"10.1001\/jama.286.24.3089","article-title":"Childhood abuse, household dysfunction, and the risk of attempted suicide throughout the life span: Findings from the adverse childhood experiences study","volume":"286","author":"Dube","year":"2001","journal-title":"JAMA"},{"key":"ref_111","first-page":"80","article-title":"Epigenetic risk factors in PTSD and depression","volume":"4","author":"Raabe","year":"2013","journal-title":"Front. Mol. Psychiatry"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/nrn2639","article-title":"Effects of stress throughout the lifespan on the brain, behaviour and cognition","volume":"10","author":"Lupien","year":"2009","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1111\/j.1469-7610.2010.02271.x","article-title":"Research Review: The neurobiology and genetics of maltreatment and adversity","volume":"51","author":"McCrory","year":"2010","journal-title":"J. Child. Psychol. Psychiatry"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.psyneuen.2004.08.003","article-title":"Stress hormones and human memory function across the lifespan","volume":"30","author":"Lupien","year":"2005","journal-title":"Psychoneuroendocrinology"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"431","DOI":"10.2217\/epi.12.34","article-title":"The lasting legacy of social stress on the epigenome of the hypothalamic\u2013pituitary\u2013adrenal axis","volume":"4","author":"Hoffmann","year":"2012","journal-title":"Epigenomics"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1111\/apha.12140","article-title":"The future is now: early life events preset adult behaviour","volume":"210","author":"Patchev","year":"2014","journal-title":"Acta. Physiol."},{"key":"ref_117","unstructured":"Fink, G. (2007). Encyclopedia of Stress, Academic Press. [2nd ed.]."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1038\/nn.2436","article-title":"Dynamic DNA methylation programs persistent adverse effects of early-life stress","volume":"12","author":"Murgatroyd","year":"2009","journal-title":"Nat. Neurosci."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Goncharova, N.D. (2013). Stress responsiveness of the hypothalamic-pituitary-adrenal axis: Age-related features of the vasopressinergic regulation. Front. Endocrinol., 4.","DOI":"10.3389\/fendo.2013.00026"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1007\/s10571-012-9842-2","article-title":"The vasopressin-deficient brattleboro rat: Lessons for the hypothalamo-pituitary-adrenal axis regulation","volume":"32","author":"Makara","year":"2012","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"2709","DOI":"10.1210\/en.2008-1211","article-title":"Postnatal glucocorticoid excess due to pituitary glucocorticoid receptor deficiency: Differential short- and long-term consequences","volume":"150","author":"Schmidt","year":"2009","journal-title":"Endocrinology"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"e90277","DOI":"10.1371\/journal.pone.0090277","article-title":"Polycomb binding precedes early-life stress responsive DNA methylation at the avp enhancer","volume":"9","author":"Murgatroyd","year":"2014","journal-title":"PLOS ONE"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"807","DOI":"10.2217\/epi.10.60","article-title":"Sex differences in brain epigenetics","volume":"2","author":"Menger","year":"2010","journal-title":"Epigenomics"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"7171","DOI":"10.1523\/JNEUROSCI.21-18-07171.2001","article-title":"Novel and transient populations of corticotropin-releasing hormone-expressing neurons in developing hippocampus suggest unique functional roles: A quantitative spatiotemporal analysis","volume":"21","author":"Chen","year":"2001","journal-title":"J. Neurosci."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"13","DOI":"10.3389\/fncel.2012.00013","article-title":"Tuning synaptic transmission in the hippocampus by stress: the CRH system","volume":"6","author":"Chen","year":"2012","journal-title":"Front. Cell. Neurosci."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.tins.2012.01.005","article-title":"Sculpting the hippocampus from within: stress, spines, and CRH","volume":"35","author":"Maras","year":"2012","journal-title":"Trends Neurosci."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"e94394","DOI":"10.1371\/journal.pone.0094394","article-title":"Epigenetic upregulation of corticotrophin-releasing hormone mediates postnatal maternal separation-induced memory deficiency","volume":"9","author":"Wang","year":"2014","journal-title":"PLOS ONE"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1210\/me.2011-1202","article-title":"V1b and CRHR1 receptor heterodimerization mediates synergistic biological actions of vasopressin and CRH","volume":"26","author":"Murat","year":"2012","journal-title":"Mol. Endocrinol."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/6\/1\/60\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:43:14Z","timestamp":1760215394000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/6\/1\/60"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,3,6]]},"references-count":128,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2015,3]]}},"alternative-id":["genes6010060"],"URL":"https:\/\/doi.org\/10.3390\/genes6010060","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,3,6]]}}}