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MeCP2: A Critical Regulator of Chromatin in Neurodevelopment and Adult Brain Function
Methyl CpG binding protein 2 (MeCP2) was first identified as a nuclear protein with a transcriptional repressor role that recognizes DNA methylation marks. MeCP2 has a well-established function in neurodevelopment, as evidenced by the severe neurological impairments characteristic of the Rett syndro...
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| Published in: | International journal of molecular sciences 2019-09, Vol.20 (18), p.4577 |
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| container_title | International journal of molecular sciences |
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| creator | Gulmez Karaca, Kubra Brito, David V C Oliveira, Ana M M |
| description | Methyl CpG binding protein 2 (MeCP2) was first identified as a nuclear protein with a transcriptional repressor role that recognizes DNA methylation marks. MeCP2 has a well-established function in neurodevelopment, as evidenced by the severe neurological impairments characteristic of the Rett syndrome (RTT) pathology and the MeCP2 duplication syndrome (MDS), caused by loss or gain of MeCP2 function, respectively. Research aimed at the underlying pathophysiological mechanisms of RTT and MDS has significantly advanced our understanding of MeCP2 functions in the nervous system. It has revealed, however, that MeCP2 has more varied and complex roles than previously thought. Here we review recent insights into the functions of MeCP2 in neurodevelopment and the less explored requirement for MeCP2 in adult brain function. We focus on the emerging view that MeCP2 is a global chromatin organizer. Finally, we discuss how the individual functions of MeCP2 in neurodevelopment and adulthood are linked to its role as a chromatin regulator. |
| doi_str_mv | 10.3390/ijms20184577 |
| format | article |
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MeCP2 has a well-established function in neurodevelopment, as evidenced by the severe neurological impairments characteristic of the Rett syndrome (RTT) pathology and the MeCP2 duplication syndrome (MDS), caused by loss or gain of MeCP2 function, respectively. Research aimed at the underlying pathophysiological mechanisms of RTT and MDS has significantly advanced our understanding of MeCP2 functions in the nervous system. It has revealed, however, that MeCP2 has more varied and complex roles than previously thought. Here we review recent insights into the functions of MeCP2 in neurodevelopment and the less explored requirement for MeCP2 in adult brain function. We focus on the emerging view that MeCP2 is a global chromatin organizer. Finally, we discuss how the individual functions of MeCP2 in neurodevelopment and adulthood are linked to its role as a chromatin regulator.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms20184577</identifier><identifier>PMID: 31527487</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>adulthood ; Adults ; Animals ; Autism ; Brain ; Brain - metabolism ; Brain - pathology ; Brain - physiopathology ; Cell Differentiation ; Chromatin ; Chromatin - genetics ; Chromatin - metabolism ; Deoxyribonucleic acid ; Diagnostic systems ; DNA ; DNA methylation ; epigenetics ; Gene expression ; Gene Expression Regulation ; Humans ; Localization ; MeCP2 ; MeCP2 protein ; Mental disorders ; Mesenchyme ; Methyl-CpG binding protein ; Methyl-CpG-Binding Protein 2 - metabolism ; Morphogenesis ; Morphology ; Mutation ; Neurodevelopment ; Neurogenesis ; Neurogenesis - genetics ; Neurological diseases ; Patients ; Protein Processing, Post-Translational ; Proteins ; Rett syndrome ; Review ; Signal Transduction ; Signs and symptoms ; Social behavior ; Stem cell transplantation ; Stem cells ; Studies ; transcriptomic profile</subject><ispartof>International journal of molecular sciences, 2019-09, Vol.20 (18), p.4577</ispartof><rights>2019. This work is licensed under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2019 by the authors. 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c478t-8d106fc199f24d500d61c9bad2bfb14f622ff07500b19a5d754c318aab5bb313</citedby><cites>FETCH-LOGICAL-c478t-8d106fc199f24d500d61c9bad2bfb14f622ff07500b19a5d754c318aab5bb313</cites><orcidid>0000-0003-4358-4846 ; 0000-0002-2729-9036 ; 0000-0002-2726-9347</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2333828555/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2333828555?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31527487$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gulmez Karaca, Kubra</creatorcontrib><creatorcontrib>Brito, David V C</creatorcontrib><creatorcontrib>Oliveira, Ana M M</creatorcontrib><title>MeCP2: A Critical Regulator of Chromatin in Neurodevelopment and Adult Brain Function</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>Methyl CpG binding protein 2 (MeCP2) was first identified as a nuclear protein with a transcriptional repressor role that recognizes DNA methylation marks. MeCP2 has a well-established function in neurodevelopment, as evidenced by the severe neurological impairments characteristic of the Rett syndrome (RTT) pathology and the MeCP2 duplication syndrome (MDS), caused by loss or gain of MeCP2 function, respectively. Research aimed at the underlying pathophysiological mechanisms of RTT and MDS has significantly advanced our understanding of MeCP2 functions in the nervous system. It has revealed, however, that MeCP2 has more varied and complex roles than previously thought. Here we review recent insights into the functions of MeCP2 in neurodevelopment and the less explored requirement for MeCP2 in adult brain function. We focus on the emerging view that MeCP2 is a global chromatin organizer. Finally, we discuss how the individual functions of MeCP2 in neurodevelopment and adulthood are linked to its role as a chromatin regulator.</description><subject>adulthood</subject><subject>Adults</subject><subject>Animals</subject><subject>Autism</subject><subject>Brain</subject><subject>Brain - metabolism</subject><subject>Brain - pathology</subject><subject>Brain - physiopathology</subject><subject>Cell Differentiation</subject><subject>Chromatin</subject><subject>Chromatin - genetics</subject><subject>Chromatin - metabolism</subject><subject>Deoxyribonucleic acid</subject><subject>Diagnostic systems</subject><subject>DNA</subject><subject>DNA methylation</subject><subject>epigenetics</subject><subject>Gene expression</subject><subject>Gene Expression Regulation</subject><subject>Humans</subject><subject>Localization</subject><subject>MeCP2</subject><subject>MeCP2 protein</subject><subject>Mental disorders</subject><subject>Mesenchyme</subject><subject>Methyl-CpG binding protein</subject><subject>Methyl-CpG-Binding Protein 2 - metabolism</subject><subject>Morphogenesis</subject><subject>Morphology</subject><subject>Mutation</subject><subject>Neurodevelopment</subject><subject>Neurogenesis</subject><subject>Neurogenesis - genetics</subject><subject>Neurological diseases</subject><subject>Patients</subject><subject>Protein Processing, Post-Translational</subject><subject>Proteins</subject><subject>Rett syndrome</subject><subject>Review</subject><subject>Signal Transduction</subject><subject>Signs and symptoms</subject><subject>Social behavior</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Studies</subject><subject>transcriptomic profile</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNpdkdtrFDEUxgdR7EXffJaALz64musk8UFYB6uFekHqcziTyzZLZrJmZgr-903dWrZCICHnx3fOd76meUHwW8Y0fhe3w0QxUVxI-ag5JpzSFcatfHzwPmpOpmmLMWVU6KfNESOCSq7kcfPrq-9-0PdojboS52ghoZ9-sySYc0E5oO6q5AHmOKJ6vvmlZOevfcq7wY8zgtGhtVvSjD4WqMDZMto55vFZ8yRAmvzzu_u0uTz7dNl9WV18_3zerS9Wlks1r5QjuA2WaB0odwJj1xKre3C0Dz3hoaU0BCxroScahJOCW0YUQC_6nhF22pzvZV2GrdmVOED5YzJE8_cjl42BUk0lb5SrnRw4JbHizAtoHShufd1Dy3RQVevDXmu39IN3ttorkB6IPqyM8cps8rVpZaulvh3m9Z1Ayb8XP81miJP1KcHo8zIZSjXVWhJNK_rqP3SblzLWTRnKGFNUCSEq9WZP2ZKnqfhwPwzB5jZ6cxh9xV8eGriH_2XNbgCKdql9</recordid><startdate>20190916</startdate><enddate>20190916</enddate><creator>Gulmez Karaca, Kubra</creator><creator>Brito, David V C</creator><creator>Oliveira, Ana M M</creator><general>MDPI AG</general><general>MDPI</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-4358-4846</orcidid><orcidid>https://orcid.org/0000-0002-2729-9036</orcidid><orcidid>https://orcid.org/0000-0002-2726-9347</orcidid></search><sort><creationdate>20190916</creationdate><title>MeCP2: A Critical Regulator of Chromatin in Neurodevelopment and Adult Brain Function</title><author>Gulmez Karaca, Kubra ; Brito, David V C ; Oliveira, Ana M M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c478t-8d106fc199f24d500d61c9bad2bfb14f622ff07500b19a5d754c318aab5bb313</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>adulthood</topic><topic>Adults</topic><topic>Animals</topic><topic>Autism</topic><topic>Brain</topic><topic>Brain - metabolism</topic><topic>Brain - pathology</topic><topic>Brain - physiopathology</topic><topic>Cell Differentiation</topic><topic>Chromatin</topic><topic>Chromatin - genetics</topic><topic>Chromatin - metabolism</topic><topic>Deoxyribonucleic acid</topic><topic>Diagnostic systems</topic><topic>DNA</topic><topic>DNA methylation</topic><topic>epigenetics</topic><topic>Gene expression</topic><topic>Gene Expression Regulation</topic><topic>Humans</topic><topic>Localization</topic><topic>MeCP2</topic><topic>MeCP2 protein</topic><topic>Mental disorders</topic><topic>Mesenchyme</topic><topic>Methyl-CpG binding protein</topic><topic>Methyl-CpG-Binding Protein 2 - metabolism</topic><topic>Morphogenesis</topic><topic>Morphology</topic><topic>Mutation</topic><topic>Neurodevelopment</topic><topic>Neurogenesis</topic><topic>Neurogenesis - genetics</topic><topic>Neurological diseases</topic><topic>Patients</topic><topic>Protein Processing, Post-Translational</topic><topic>Proteins</topic><topic>Rett syndrome</topic><topic>Review</topic><topic>Signal Transduction</topic><topic>Signs and symptoms</topic><topic>Social behavior</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><topic>Studies</topic><topic>transcriptomic profile</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gulmez Karaca, Kubra</creatorcontrib><creatorcontrib>Brito, David V C</creatorcontrib><creatorcontrib>Oliveira, Ana M M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest - Health & Medical Complete保健、医学与药学数据库</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Open Access Journals</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gulmez Karaca, Kubra</au><au>Brito, David V C</au><au>Oliveira, Ana M M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MeCP2: A Critical Regulator of Chromatin in Neurodevelopment and Adult Brain Function</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2019-09-16</date><risdate>2019</risdate><volume>20</volume><issue>18</issue><spage>4577</spage><pages>4577-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>Methyl CpG binding protein 2 (MeCP2) was first identified as a nuclear protein with a transcriptional repressor role that recognizes DNA methylation marks. MeCP2 has a well-established function in neurodevelopment, as evidenced by the severe neurological impairments characteristic of the Rett syndrome (RTT) pathology and the MeCP2 duplication syndrome (MDS), caused by loss or gain of MeCP2 function, respectively. Research aimed at the underlying pathophysiological mechanisms of RTT and MDS has significantly advanced our understanding of MeCP2 functions in the nervous system. It has revealed, however, that MeCP2 has more varied and complex roles than previously thought. Here we review recent insights into the functions of MeCP2 in neurodevelopment and the less explored requirement for MeCP2 in adult brain function. We focus on the emerging view that MeCP2 is a global chromatin organizer. Finally, we discuss how the individual functions of MeCP2 in neurodevelopment and adulthood are linked to its role as a chromatin regulator.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>31527487</pmid><doi>10.3390/ijms20184577</doi><orcidid>https://orcid.org/0000-0003-4358-4846</orcidid><orcidid>https://orcid.org/0000-0002-2729-9036</orcidid><orcidid>https://orcid.org/0000-0002-2726-9347</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | adulthood Adults Animals Autism Brain Brain - metabolism Brain - pathology Brain - physiopathology Cell Differentiation Chromatin Chromatin - genetics Chromatin - metabolism Deoxyribonucleic acid Diagnostic systems DNA DNA methylation epigenetics Gene expression Gene Expression Regulation Humans Localization MeCP2 MeCP2 protein Mental disorders Mesenchyme Methyl-CpG binding protein Methyl-CpG-Binding Protein 2 - metabolism Morphogenesis Morphology Mutation Neurodevelopment Neurogenesis Neurogenesis - genetics Neurological diseases Patients Protein Processing, Post-Translational Proteins Rett syndrome Review Signal Transduction Signs and symptoms Social behavior Stem cell transplantation Stem cells Studies transcriptomic profile |
| title | MeCP2: A Critical Regulator of Chromatin in Neurodevelopment and Adult Brain Function |
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