{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T10:18:33Z","timestamp":1792145913598,"version":"4.4.0"},"reference-count":39,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5646","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2003,10,31]]},"abstract":"<jats:p>\n                    Mutations in\n                    <jats:italic>MeCP2<\/jats:italic>\n                    , which encodes a protein that has been proposed to function as a global transcriptional repressor, are the cause of Rett syndrome (RT T), an X-linked progressive neurological disorder. Although the selective inactivation of MeCP2 in neurons is sufficient to confer a Rett-like phenotype in mice, the specific functions of MeCP2 in postmitotic neurons are not known. We find that MeCP2 binds selectively to\n                    <jats:italic>BDNF<\/jats:italic>\n                    promoter III and functions to repress expression of the\n                    <jats:italic>BDNF<\/jats:italic>\n                    gene. Membrane depolarization triggers the calcium-dependent phosphorylation and release of MeCP2 from\n                    <jats:italic>BDNF<\/jats:italic>\n                    promoter III, thereby facilitating transcription. These studies indicate that MeCP2 plays a key role in the control of neuronal activity\u2013dependent gene regulation and suggest that the deregulation of this process may underlie the pathology of RT T.\n                  <\/jats:p>","DOI":"10.1126\/science.1086446","type":"journal-article","created":{"date-parts":[[2003,10,30]],"date-time":"2003-10-30T20:25:22Z","timestamp":1067545522000},"page":"885-889","source":"Crossref","is-referenced-by-count":1072,"title":["Derepression of BDNF Transcription Involves Calcium-Dependent Phosphorylation of MeCP2"],"prefix":"10.1126","volume":"302","author":[{"given":"Wen G.","family":"Chen","sequence":"first","affiliation":[{"name":"Division of Neuroscience, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA."},{"name":"Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115, USA."},{"name":"Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA."},{"name":"Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Chang","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA."},{"name":"Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115, USA."},{"name":"Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA."},{"name":"Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingxi","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA."},{"name":"Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115, USA."},{"name":"Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA."},{"name":"Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Meissner","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA."},{"name":"Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115, USA."},{"name":"Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA."},{"name":"Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne E.","family":"West","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA."},{"name":"Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115, USA."},{"name":"Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA."},{"name":"Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric C.","family":"Griffith","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA."},{"name":"Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115, USA."},{"name":"Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA."},{"name":"Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf","family":"Jaenisch","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA."},{"name":"Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115, USA."},{"name":"Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA."},{"name":"Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael E.","family":"Greenberg","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA."},{"name":"Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115, USA."},{"name":"Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA."},{"name":"Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, 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and methods are available as supporting material on Science Online."},{"key":"e_1_3_1_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/30.5.1139"},{"key":"e_1_3_1_32_2","unstructured":"W. G. Chen unpublished observations."},{"key":"e_1_3_1_33_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M210256200"},{"key":"e_1_3_1_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-0674(02)00335-6"},{"key":"e_1_3_1_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)00655-4"},{"key":"e_1_3_1_36_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8097062"},{"key":"e_1_3_1_37_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/21.21.4886"},{"key":"e_1_3_1_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/311433a0"},{"key":"e_1_3_1_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)47394-8"},{"key":"e_1_3_1_40_2","unstructured":"We particularly thank K. H. Wang for thoughtful discussions; J. Zieg for critical reading of the manuscript; J. Z. Zhou Y. C. Ma and S. Paradis for sharing precious reagents; L. S. Hu for preparing the C-MeCP2 antibody; and Y. E. Sun for communicating unpublished observations. M.E.G. acknowledges the generous support of the F. M. Kirby Foundation to the Division of Neuroscience. Supported by a Mental Retardation Research Center grant (HD 18655) and a NIH grant (NS28829) to M.E.G. W.G.C. is a Howard Hughes Medical Institute predoctoral fellow A.E.W. is supported by a fellowship from the Charles A. King Trust of the Medical Foundation and E.C.G. is a Helen Hay Whitney postdoctoral fellow. R.J. and Q.C. acknowledge support from the Rett Syndrome Research Foundation and A.M. is supported by a predoctoral fellowship from the Boehringer Ingelheim Funds."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1086446","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T22:22:56Z","timestamp":1704838976000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1086446"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,10,31]]},"references-count":39,"journal-issue":{"issue":"5646","published-print":{"date-parts":[[2003,10,31]]}},"alternative-id":["10.1126\/science.1086446"],"URL":"https:\/\/doi.org\/10.1126\/science.1086446","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1016159.200100","asserted-by":"object"}]},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,10,31]]}}}