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rdf:type |
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lifeskim:mentions |
umls-concept:C0002860,
umls-concept:C0039082,
umls-concept:C0086418,
umls-concept:C0205182,
umls-concept:C0208973,
umls-concept:C0441712,
umls-concept:C0524637,
umls-concept:C1156205,
umls-concept:C1412697,
umls-concept:C1514562,
umls-concept:C1517892,
umls-concept:C1524062,
umls-concept:C1704666,
umls-concept:C1720086,
umls-concept:C1880389,
umls-concept:C1883204,
umls-concept:C1883221,
umls-concept:C1883712
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pubmed:issue |
7
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pubmed:dateCreated |
2011-7-6
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pubmed:abstractText |
ATR-X (alpha-thalassemia/mental retardation, X-linked) syndrome is a human congenital disorder that causes severe intellectual disabilities. Mutations in the ATRX gene, which encodes an ATP-dependent chromatin-remodeler, are responsible for the syndrome. Approximately 50% of the missense mutations in affected persons are clustered in a cysteine-rich domain termed ADD (ATRX-DNMT3-DNMT3L, ADD(ATRX)), whose function has remained elusive. Here we identify ADD(ATRX) as a previously unknown histone H3-binding module, whose binding is promoted by lysine 9 trimethylation (H3K9me3) but inhibited by lysine 4 trimethylation (H3K4me3). The cocrystal structure of ADD(ATRX) bound to H3(1-15)K9me3 peptide reveals an atypical composite H3K9me3-binding pocket, which is distinct from the conventional trimethyllysine-binding aromatic cage. Notably, H3K9me3-pocket mutants and ATR-X syndrome mutants are defective in both H3K9me3 binding and localization at pericentromeric heterochromatin; thus, we have discovered a unique histone-recognition mechanism underlying the ATR-X etiology.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1545-9985
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pubmed:author |
pubmed-author:AllisC DavidCD,
pubmed-author:CochraneJesse CJC,
pubmed-author:GhoshSharmisthaS,
pubmed-author:IwaseShigekiS,
pubmed-author:LewisPeter WPW,
pubmed-author:LiHaitaoH,
pubmed-author:PatelDinshaw JDJ,
pubmed-author:PickettsDavid JDJ,
pubmed-author:ShiYangY,
pubmed-author:TengT KTK,
pubmed-author:XiangBinB
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pubmed:issnType |
Electronic
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pubmed:volume |
18
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
769-76
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:21666679-Amino Acid Sequence,
pubmed-meshheading:21666679-Binding Sites,
pubmed-meshheading:21666679-DNA Helicases,
pubmed-meshheading:21666679-Heterochromatin,
pubmed-meshheading:21666679-Histones,
pubmed-meshheading:21666679-Humans,
pubmed-meshheading:21666679-Intellectual Disability,
pubmed-meshheading:21666679-Methylation,
pubmed-meshheading:21666679-Models, Molecular,
pubmed-meshheading:21666679-Molecular Sequence Data,
pubmed-meshheading:21666679-Nuclear Proteins,
pubmed-meshheading:21666679-Protein Interaction Mapping,
pubmed-meshheading:21666679-Protein Structure, Tertiary,
pubmed-meshheading:21666679-Sequence Alignment
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pubmed:year |
2011
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pubmed:articleTitle |
ATRX ADD domain links an atypical histone methylation recognition mechanism to human mental-retardation syndrome.
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pubmed:affiliation |
Division of Newborn Medicine, Department of Medicine, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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