{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:54:36Z","timestamp":1790834076275,"version":"4.1.0"},"reference-count":70,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T00:00:00Z","timestamp":1670544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Sciences and Engineering Research Council of Canada (NSERC)","award":["RGPIN-2016-06035"],"award-info":[{"award-number":["RGPIN-2016-06035"]}]},{"name":"Natural Sciences and Engineering Research Council of Canada (NSERC)","award":["202203PJG-482520-CIA-CDAA-111824"],"award-info":[{"award-number":["202203PJG-482520-CIA-CDAA-111824"]}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research (CIHR)","doi-asserted-by":"publisher","award":["RGPIN-2016-06035"],"award-info":[{"award-number":["RGPIN-2016-06035"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research (CIHR)","doi-asserted-by":"publisher","award":["202203PJG-482520-CIA-CDAA-111824"],"award-info":[{"award-number":["202203PJG-482520-CIA-CDAA-111824"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Methyl CpG binding protein 2 (MeCP2) is an epigenetic reader that binds to methylated CpG dinucleotides and regulates gene transcription. Mecp2\/MECP2 gene has 4 exons, encoding for protein isoforms MeCP2E1 and MeCP2E2. MeCP2 plays key roles in neurodevelopment, therefore, its gain- and loss-of-function mutations lead to neurodevelopmental disorders including Rett Syndrome. Here, we describe the structure, functional domains, and evidence support for potential additional alternatively spliced MECP2 transcripts and protein isoforms. We conclude that NCBI MeCP2 isoforms 3 and 4 contain certain MeCP2 functional domains. Our in silico analysis led to identification of histone modification and accessibility profiles at the MECP2 gene and its cis-regulatory elements. We conclude that the human MECP2 gene associated histone post-translational modifications exhibit high similarity between males and females. Between brain regions, histone modifications were found to be less conserved and enriched within larger genomic segments named as \u201cS1\u2013S11\u201d. We also identified highly conserved DNA accessibility regions in different tissues and brain regions, named as \u201cA1\u2013A9\u201d and \u201cB1\u2013B9\u201d. DNA methylation profile was similar between mid-frontal gyrus of donors 35 days\u201325 years of age. Based on ATAC-seq data, the identified hypomethylated regions \u201cH1\u2013H8\u201d intersected with most regions of the accessible chromatin (A regions).<\/jats:p>","DOI":"10.3390\/ijms232415643","type":"journal-article","created":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T01:42:27Z","timestamp":1670809347000},"page":"15643","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The Chromatin Structure at the MECP2 Gene and In Silico Prediction of Potential Coding and Non-Coding MECP2 Splice Variants"],"prefix":"10.3390","volume":"23","author":[{"given":"Danilo","family":"Shevkoplyas","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen My","family":"Vuu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R.","family":"Davie","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3619-6116","authenticated-orcid":false,"given":"Mojgan","family":"Rastegar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1016\/j.tig.2018.03.007","article-title":"The Evolution of Gene Expression in cis and trans","volume":"34","author":"Signor","year":"2018","journal-title":"Trends Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.tig.2020.09.018","article-title":"Gene Regulation and Cellular Metabolism: An Essential Partnership","volume":"37","author":"Carthew","year":"2021","journal-title":"Trends Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"151237","DOI":"10.1016\/j.ejcb.2022.151237","article-title":"MeCP2 and transcriptional control of eukaryotic gene expression","volume":"101","author":"Buist","year":"2022","journal-title":"Eur. J. Cell Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/978-1-60761-854-6_3","article-title":"Regulatory regions in DNA: Promoters, enhancers, silencers, and insulators","volume":"674","author":"Riethoven","year":"2010","journal-title":"Methods Mol. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1042\/bj3340565","article-title":"Hepatocyte nuclear factor 6: Organization and chromosomal assignment of the rat gene and characterization of its promoter","volume":"334","author":"Rastegar","year":"1998","journal-title":"Biochem. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1756-8935-5-1","article-title":"Enhancers and silencers: An integrated and simple model for their function","volume":"5","author":"Kolovos","year":"2012","journal-title":"Epigenetics Chromatin"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"9243","DOI":"10.1073\/pnas.142291299","article-title":"Promoter-proximal tethering elements regulate enhancer-promoter specificity in the Drosophila Antennapedia complex","volume":"99","author":"Calhoun","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1002\/jcp.21678","article-title":"Epigenetic control","volume":"219","author":"Delcuve","year":"2009","journal-title":"J. Cell Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"670","DOI":"10.3390\/biology3040670","article-title":"DNA modifications: Function and applications in normal and disease States","volume":"3","author":"Liyanage","year":"2014","journal-title":"Biology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"755076","DOI":"10.3389\/fgene.2021.755076","article-title":"Editorial: Epigenetic Mechanisms and Their Involvement in Rare Diseases","volume":"12","author":"Rastegar","year":"2021","journal-title":"Front. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.ejphar.2018.08.021","article-title":"Epigenetic tools (The Writers, The Readers and The Erasers) and their implications in cancer therapy","volume":"837","author":"Biswas","year":"2018","journal-title":"Eur. J. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Marzban, H. (2017). Epigenetics and Cerebellar Neurodevelopmental Disorders. Development of the Cerebellum from Molecular Aspects to Diseases, Springer International Publishing.","DOI":"10.1007\/978-3-319-59749-2"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1038\/ng1327","article-title":"A previously unidentified MECP2 open reading frame defines a new protein isoform relevant to Rett syndrome","volume":"36","author":"Mnatzakanian","year":"2004","journal-title":"Nat. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"R89","DOI":"10.1093\/hmg\/ddaa154","article-title":"Regulation, diversity and function of MECP2 exon and 3\u2019UTR isoforms","volume":"29","author":"Rodrigues","year":"2020","journal-title":"Hum. Mol. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/0092-8674(92)90610-O","article-title":"Purification, sequence, and cellular localization of a novel chromosomal protein that binds to methylated DNA","volume":"69","author":"Lewis","year":"1992","journal-title":"Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/0092-8674(89)90430-3","article-title":"Identification of a mammalian protein that binds specifically to DNA containing methylated CpGs","volume":"58","author":"Meehan","year":"1989","journal-title":"Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1016\/j.cell.2012.11.022","article-title":"MeCP2 binds to 5hmC enriched within active genes and accessible chromatin in the nervous system","volume":"151","author":"Mellen","year":"2012","journal-title":"Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5085","DOI":"10.1093\/nar\/20.19.5085","article-title":"Characterization of MeCP2, a vertebrate DNA binding protein with affinity for methylated DNA","volume":"20","author":"Meehan","year":"1992","journal-title":"Nucleic Acids Res."},{"key":"ref_19","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_20","doi-asserted-by":"crossref","first-page":"2201","DOI":"10.1093\/nar\/28.10.2201","article-title":"Histone deacetylase-independent transcriptional repression by methyl-CpG-binding protein 2","volume":"28","author":"Yu","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_21","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_22","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1038\/nn.3434","article-title":"Rett syndrome mutations abolish the interaction of MeCP2 with the NCoR\/SMRT co-repressor","volume":"16","author":"Lyst","year":"2013","journal-title":"Nat. Neurosci."},{"key":"ref_23","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_24","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_25","doi-asserted-by":"crossref","first-page":"1921","DOI":"10.1093\/nar\/28.9.1921","article-title":"MeCP2 driven transcriptional repression in vitro: Selectivity for methylated DNA, action at a distance and contacts with the basal transcription machinery","volume":"28","author":"Kaludov","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.stem.2013.09.001","article-title":"Global transcriptional and translational repression in human-embryonic-stem-cell-derived Rett syndrome neurons","volume":"13","author":"Li","year":"2013","journal-title":"Cell Stem Cell"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Buist, M., El Tobgy, N., Shevkoplyas, D., Genung, M., Sher, A.A., Pejhan, S., and Rastegar, M. (2022). Differential Sensitivity of the Protein Translation Initiation Machinery and mTOR Signaling to MECP2 Gain- and Loss-of-Function Involves MeCP2 Isoform-Specific Homeostasis in the Brain. Cells, 11.","DOI":"10.3390\/cells11091442"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"635","DOI":"10.3389\/fgene.2018.00635","article-title":"MECP2 Mutation Interrupts Nucleolin-mTOR-P70S6K Signaling in Rett Syndrome Patients","volume":"9","author":"Olson","year":"2018","journal-title":"Front. Genet."},{"key":"ref_29","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_30","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_31","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.expneurol.2015.01.006","article-title":"Ethanol deregulates Mecp2\/MeCP2 in differentiating neural stem cells via interplay between 5-methylcytosine and 5-hydroxymethylcytosine at the Mecp2 regulatory elements","volume":"265","author":"Liyanage","year":"2015","journal-title":"Exp. Neurol"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1038\/s41598-018-36059-y","article-title":"Genome-Wide Transcriptome Landscape of Embryonic Brain-Derived Neural Stem Cells Exposed to Alcohol with Strain-Specific Cross-Examination in BL6 and CD1 Mice","volume":"9","author":"Xu","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Zachariah, R.M., Olson, C.O., Ezeonwuka, C., and Rastegar, M. (2012). Novel MeCP2 isoform-specific antibody reveals the endogenous MeCP2E1 expression in murine brain, primary neurons and astrocytes. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0049763"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Liyanage, V.R.B., Olson, C.O., Zachariah, R.M., Davie, J.R., and Rastegar, M. (2019). DNA Methylation Contributes to the Differential Expression Levels of Mecp2 in Male Mice Neurons and Astrocytes. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20081845"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/2040-2392-4-46","article-title":"Decitabine alters the expression of Mecp2 isoforms via dynamic DNA methylation at the Mecp2 regulatory elements in neural stem cells","volume":"4","author":"Liyanage","year":"2013","journal-title":"Mol. Autism"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Olson, C.O., Zachariah, R.M., Ezeonwuka, C.D., Liyanage, V.R., and Rastegar, M. (2014). Brain region-specific expression of MeCP2 isoforms correlates with DNA methylation within Mecp2 regulatory elements. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0090645"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Pejhan, S., and Rastegar, M. (2021). Role of DNA Methyl-CpG-Binding Protein MeCP2 in Rett Syndrome Pathobiology and Mechanism of Disease. Biomolecules, 11.","DOI":"10.3390\/biom11010075"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"763","DOI":"10.3389\/fcell.2020.00763","article-title":"The MeCP2E1\/E2-BDNF-miR132 Homeostasis Regulatory Network Is Region-Dependent in the Human Brain and Is Impaired in Rett Syndrome Patients","volume":"8","author":"Pejhan","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"415825","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_40","doi-asserted-by":"crossref","unstructured":"Buist, M., Fuss, D., and Rastegar, M. (2021). Transcriptional Regulation of MECP2E1-E2 Isoforms and BDNF by Metformin and Simvastatin through Analyzing Nascent RNA Synthesis in a Human Brain Cell Line. Biomolecules, 11.","DOI":"10.3390\/biom11081253"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/13810","article-title":"Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2","volume":"23","author":"Amir","year":"1999","journal-title":"Nat. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s12017-014-8295-9","article-title":"Rett syndrome and MeCP2","volume":"16","author":"Liyanage","year":"2014","journal-title":"Neuromol. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"38590","DOI":"10.1038\/srep38590","article-title":"From Function to Phenotype: Impaired DNA Binding and Clustering Correlates with Clinical Severity in Males with Missense Mutations in MECP2","volume":"6","author":"Sheikh","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1111\/nan.12619","article-title":"Differential brain region-specific expression of MeCP2 and BDNF in Rett Syndrome patients: A distinct grey-white matter variation","volume":"46","author":"Pejhan","year":"2020","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1002\/ana.410140412","article-title":"A progressive syndrome of autism, dementia, ataxia, and loss of purposeful hand use in girls: Rett\u2019s syndrome: Report of 35 cases","volume":"14","author":"Hagberg","year":"1983","journal-title":"Ann. Neurol"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1002\/ajmg.a.33184","article-title":"The MECP2 duplication syndrome","volume":"152","author":"Ramocki","year":"2010","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_47","unstructured":"(2022, October 01). The NCBI Handbook [Internet]; 2nd ed.; National Center for Biotechnology Information (US): Bethesda (MD, USA), Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK143764\/."},{"key":"ref_48","first-page":"D682","article-title":"Ensembl 2020","volume":"48","author":"Yates","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2699","DOI":"10.1093\/nar\/gky092","article-title":"UniProt: The universal protein knowledgebase","volume":"46","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1101\/gr.229102","article-title":"The human genome browser at UCSC","volume":"12","author":"Kent","year":"2002","journal-title":"Genome Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/nbt.1754","article-title":"Integrative genomics viewer","volume":"29","author":"Robinson","year":"2011","journal-title":"Nat. Biotechnol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1818","DOI":"10.1093\/nar\/gkh349","article-title":"The major form of MeCP2 has a novel N-terminus generated by alternative splicing","volume":"32","author":"Kriaucionis","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2447","DOI":"10.1093\/hmg\/ddt640","article-title":"Mice with an isoform-ablating Mecp2 exon 1 mutation recapitulate the neurologic deficits of Rett syndrome","volume":"23","author":"Yasui","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1186\/s13072-019-0298-1","article-title":"MeCP2-E1 isoform is a dynamically expressed, weakly DNA-bound protein with different protein and DNA interactions compared to MeCP2-E2","volume":"12","author":"Khajavi","year":"2019","journal-title":"Epigenetics Chromatin"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1093\/hmg\/ddl099","article-title":"Identification of cis-regulatory elements for MECP2 expression","volume":"15","author":"Liu","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"13859","DOI":"10.1074\/jbc.M111.309864","article-title":"Methyl CpG-binding protein isoform MeCP2_e2 is dispensable for Rett syndrome phenotypes but essential for embryo viability and placenta development","volume":"287","author":"Itoh","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"21931","DOI":"10.1073\/pnas.1016071107","article-title":"Histone H3K27ac separates active from poised enhancers and predicts developmental state","volume":"107","author":"Creyghton","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/ncb1076","article-title":"Histone H3 lysine 4 methylation patterns in higher eukaryotic genes","volume":"6","author":"Schneider","year":"2004","journal-title":"Nat. Cell Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1038\/nsmb.1659","article-title":"Chromatin organization marks exon-intron structure","volume":"16","author":"Schwartz","year":"2009","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1126\/science.1076997","article-title":"Role of histone H3 lysine 27 methylation in Polycomb-group silencing","volume":"298","author":"Cao","year":"2002","journal-title":"Science"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"D1186","DOI":"10.1093\/nar\/gky1036","article-title":"ECO, the Evidence & Conclusion Ontology: Community standard for evidence information","volume":"47","author":"Giglio","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"W597-600","DOI":"10.1093\/nar\/gkt376","article-title":"Analysis Tool Web Services from the EMBL-EBI","volume":"41","author":"McWilliam","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3784","DOI":"10.1093\/nar\/gkg563","article-title":"ExPASy: The proteomics server for in-depth protein knowledge and analysis","volume":"31","author":"Gasteiger","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"4886","DOI":"10.1093\/nar\/21.21.4886","article-title":"Dissection of the methyl-CpG binding domain from the chromosomal protein MeCP2","volume":"21","author":"Nan","year":"1993","journal-title":"Nucleic Acids Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"15057","DOI":"10.1074\/jbc.M700855200","article-title":"Intrinsic disorder and autonomous domain function in the multifunctional nuclear protein, MeCP2","volume":"282","author":"Adams","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_66","first-page":"656","article-title":"BLAT--the BLAST-like alignment tool","volume":"12","author":"Kent","year":"2002","journal-title":"Genome Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1093\/nar\/30.1.207","article-title":"Gene Expression Omnibus: NCBI gene expression and hybridization array data repository","volume":"30","author":"Edgar","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nature11247","article-title":"An integrated encyclopedia of DNA elements in the human genome","volume":"489","author":"Consortium","year":"2012","journal-title":"Nature"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"D794","DOI":"10.1093\/nar\/gkx1081","article-title":"The Encyclopedia of DNA elements (ENCODE): Data portal update","volume":"46","author":"Davis","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1237905","DOI":"10.1126\/science.1237905","article-title":"Global epigenomic reconfiguration during mammalian brain development","volume":"341","author":"Lister","year":"2013","journal-title":"Science"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/24\/15643\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:37:35Z","timestamp":1760146655000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/24\/15643"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,9]]},"references-count":70,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["ijms232415643"],"URL":"https:\/\/doi.org\/10.3390\/ijms232415643","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,9]]}}}