{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T10:12:54Z","timestamp":1792145574098,"version":"4.4.0"},"reference-count":36,"publisher":"National Academy of Sciences","issue":"12","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,3,24]]},"abstract":"<jats:p>\n                    Mutations of\n                    <jats:italic>MECP2<\/jats:italic>\n                    (\n                    <jats:italic>Methyl-CpG Binding Protein 2<\/jats:italic>\n                    ) cause Rett syndrome. As a chromatin-associated multifunctional protein, how MeCP2 integrates external signals and regulates neuronal function remain unclear. Although neuronal activity-induced phosphorylation of MeCP2 at serine 421 (S421) has been reported, the full spectrum of MeCP2 phosphorylation together with the in vivo function of such modifications are yet to be revealed. Here, we report the identification of several MeCP2 phosphorylation sites in normal and epileptic brains from multiple species. We demonstrate that serine 80 (S80) phosphorylation of MeCP2 is critical as its mutation into alanine (S80A) in transgenic knock-in mice leads to locomotor deficits. S80A mutation attenuates MeCP2 chromatin association at several gene promoters in resting neurons and leads to transcription changes of a small number of genes. Calcium influx in neurons causes dephosphorylation at S80, potentially contributing to its dissociation from the chromatin. We postulate that phosphorylation of MeCP2 modulates its dynamic function in neurons transiting between resting and active states within neural circuits that underlie behaviors.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0811648106","type":"journal-article","created":{"date-parts":[[2009,2,18]],"date-time":"2009-02-18T21:40:55Z","timestamp":1234993255000},"page":"4882-4887","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":211,"title":["Phosphorylation of MeCP2 at Serine 80 regulates its chromatin association and neurological function"],"prefix":"10.1073","volume":"106","author":[{"given":"Jifang","family":"Tao","sequence":"first","affiliation":[{"name":"Departments of Molecular and Medical Pharmacology and Psychiatry and Behavioral Sciences, University of California, Los Angeles, CA 90095;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keping","family":"Hu","sequence":"additional","affiliation":[{"name":"National Institute on Aging, Baltimore, MD 21224;"},{"name":"Nemours Biomedical Research, Alfred I. duPont Hospital for Children, Wilmington, DE 19803; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Chang","sequence":"additional","affiliation":[{"name":"Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wu","sequence":"additional","affiliation":[{"name":"Departments of Molecular and Medical Pharmacology and Psychiatry and Behavioral Sciences, University of California, Los Angeles, CA 90095;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas E.","family":"Sherman","sequence":"additional","affiliation":[{"name":"W. M. Keck Biomedical Mass Spectrometry Lab, Department of Microbiology, University of Virginia, Charlottesville, VA 22908;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keri","family":"Martinowich","sequence":"additional","affiliation":[{"name":"Departments of Molecular and Medical Pharmacology and Psychiatry and Behavioral Sciences, University of California, Los Angeles, CA 90095;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Klose","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Oxford University, Oxford OX1 3QU, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn","family":"Schanen","sequence":"additional","affiliation":[{"name":"Nemours Biomedical Research, Alfred I. duPont Hospital for Children, Wilmington, DE 19803; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf","family":"Jaenisch","sequence":"additional","affiliation":[{"name":"Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weidong","family":"Wang","sequence":"additional","affiliation":[{"name":"National Institute on Aging, Baltimore, MD 21224;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi Eve","family":"Sun","sequence":"additional","affiliation":[{"name":"Departments of Molecular and Medical Pharmacology and Psychiatry and Behavioral Sciences, University of California, Los Angeles, CA 90095;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,3,24]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.191352298"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-4388(00)00090-8"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/35077089"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.06.002"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn0602-855"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5272-05.2006"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.01656"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/13810"},{"key":"e_1_3_3_9_2","first-page":"723","article-title":"On a unusual brain atrophy syndrome in hyperammonemia in childhood","volume":"116","author":"Rett A","year":"1966","unstructured":"A Rett, On a unusual brain atrophy syndrome in hyperammonemia in childhood. Wien Med Wochenschr 116, 723\u2013726, in German. (1966).","journal-title":"Wien Med Wochenschr"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410140412"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/85906"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/85899"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1138389"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/30764"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2005.07.021"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0507856102"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01593-06"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M305308200"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2004.07.006"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/64.6.537"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00826.2007"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2006.02.062"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.08.018"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506071102"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1153252"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2006.09.037"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0906-962"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.08.021"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(99)00131-X"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81816-4"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)00654-2"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1090842"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.03.013"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2350-8-36"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.242566899"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3553-05.2006"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0811648106","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T17:33:56Z","timestamp":1649784836000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0811648106"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,3,24]]},"references-count":36,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2009,3,24]]}},"alternative-id":["10.1073\/pnas.0811648106"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0811648106","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,3,24]]},"assertion":[{"value":"2008-11-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2009-03-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}