{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T10:09:56Z","timestamp":1792145396599,"version":"4.4.0"},"reference-count":24,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5880","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2008,5,30]]},"abstract":"<jats:p>\n                    Mutations in the gene encoding the transcriptional repressor methyl-CpG binding protein 2 (MeCP2) cause the neurodevelopmental disorder Rett syndrome. Loss of function as well as increased dosage of the\n                    <jats:italic>MECP2<\/jats:italic>\n                    gene cause a host of neuropsychiatric disorders. To explore the molecular mechanism(s) underlying these disorders, we examined gene expression patterns in the hypothalamus of mice that either lack or overexpress MeCP2. In both models, MeCP2 dysfunction induced changes in the expression levels of thousands of genes, but unexpectedly the majority of genes (\u223c85%) appeared to be activated by MeCP2. We selected six genes and confirmed that MeCP2 binds to their promoters. Furthermore, we showed that MeCP2 associates with the transcriptional activator CREB1 at the promoter of an activated target but not a repressed target. These studies suggest that MeCP2 regulates the expression of a wide range of genes in the hypothalamus and that it can function as both an activator and a repressor of transcription.\n                  <\/jats:p>","DOI":"10.1126\/science.1153252","type":"journal-article","created":{"date-parts":[[2008,5,29]],"date-time":"2008-05-29T16:53:48Z","timestamp":1212080028000},"page":"1224-1229","source":"Crossref","is-referenced-by-count":1614,"title":["MeCP2, a Key Contributor to Neurological Disease, Activates and Represses Transcription"],"prefix":"10.1126","volume":"320","author":[{"given":"Maria","family":"Chahrour","sequence":"first","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Center for Molecular Discovery, Departments of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Center for Bioinformatics, The Methodist Hospital Research Institute and Weill Cornell College of Medicine, Houston, TX 77030, USA."},{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung Yun","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Center for Molecular Discovery, Departments of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Center for Bioinformatics, The Methodist Hospital Research Institute and Weill Cornell College of Medicine, Houston, TX 77030, USA."},{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad","family":"Shaw","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Center for Molecular Discovery, Departments of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Center for Bioinformatics, The Methodist Hospital Research Institute and Weill Cornell College of Medicine, Houston, TX 77030, USA."},{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobo","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Center for Molecular Discovery, Departments of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Center for Bioinformatics, The Methodist Hospital Research Institute and Weill Cornell College of Medicine, Houston, TX 77030, USA."},{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen T. C.","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Center for Molecular Discovery, Departments of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Center for Bioinformatics, The Methodist Hospital Research Institute and Weill Cornell College of Medicine, Houston, TX 77030, USA."},{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Center for Molecular Discovery, Departments of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Center for Bioinformatics, The Methodist Hospital Research Institute and Weill Cornell College of Medicine, Houston, TX 77030, USA."},{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huda Y.","family":"Zoghbi","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Center for Molecular Discovery, Departments of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Center for Bioinformatics, The Methodist Hospital Research Institute and Weill Cornell College of Medicine, Houston, TX 77030, USA."},{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/13810"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2006.04.009"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/85899"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh282"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/30764"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/561"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.08.018"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.242566899"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2005-3032"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-7-325"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2005.09.007"},{"key":"e_1_3_1_13_2","unstructured":"Materials and methods are available as supporting material on Science Online."},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2006.09.037"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10038-004-0145-4"},{"key":"e_1_3_1_16_2","first-page":"869","volume":"144","year":"2007","unstructured":"C. L. Martinet al., Am. J. Med. Genet. B. Neuropsychiatr. Genet.144, 869 (2007).","journal-title":"Am. J. Med. Genet. B. Neuropsychiatr. Genet."},{"key":"e_1_3_1_17_2","first-page":"122","volume":"133","year":"2005","unstructured":"H. Caldeira Araujoet al., Am. J. Med. Genet. A.133, 122 (2005).","journal-title":"Am. J. Med. Genet. A."},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-006-0340-8"},{"key":"e_1_3_1_19_2","doi-asserted-by":"crossref","first-page":"875","DOI":"10.18388\/abp.2004_3520","volume":"51","year":"2004","unstructured":"J. Sykut-Cegielska, W. Gradowska, S. Mercimek-Mahmutoglu, S. Stockler-Ipsiroglu, Acta Biochim. Pol.51, 875 (2004).","journal-title":"Acta Biochim. Pol."},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn2010"},{"key":"e_1_3_1_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0707442104"},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1086446"},{"key":"e_1_3_1_23_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1090842"},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.12.027"},{"key":"e_1_3_1_25_2","unstructured":"We thank members of the Zoghbi laboratory for their thoughtful comments Z. Yin for technical assistance M. Shinawi and A. Tawil for technical advice Y. Klisch for the art work and J. Lim J. Neul and M. Greenberg for reagents. The Baylor College of Medicine Microarray Core Facility performed the microarray experiments. This work was funded by NIH\/National Institute of Neurological Disorders and Stroke grant NS057819 (H.Z.) National Institute of Child Health and Human Development Mental Retardation and Developmental Disabilities Research Center HD024064 (H.Z.) the International Rett Syndrome Foundation and the Simons Foundation. H.Z. is a Howard Hughes Medical Institute investigator. The microarray data have been deposited in the National Center for Biotechnology Information Gene Expression Omnibus (GEO) (www.ncbi.nlm.nih.gov\/geo) and are accessible through GEO Series accession number GSE11150."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1153252","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T08:34:47Z","timestamp":1738226087000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1153252"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,5,30]]},"references-count":24,"journal-issue":{"issue":"5880","published-print":{"date-parts":[[2008,5,30]]}},"alternative-id":["10.1126\/science.1153252"],"URL":"https:\/\/doi.org\/10.1126\/science.1153252","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1116195.572191","asserted-by":"object"}]},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,5,30]]}}}