DC Field | Value | Language |
---|---|---|
dc.contributor.author | Seong, Ihn Sik | ko |
dc.contributor.author | Woda, Juliana M. | ko |
dc.contributor.author | Song, Ji-Joon | ko |
dc.contributor.author | Lloret, Alejandro | ko |
dc.contributor.author | Abeyrathne, Priyanka D. | ko |
dc.contributor.author | Woo, Caroline J. | ko |
dc.contributor.author | Gregory, Gillian | ko |
dc.contributor.author | Lee, Jong-Min | ko |
dc.contributor.author | Wheeler, Vanessa C. | ko |
dc.contributor.author | Walz, Thomas | ko |
dc.contributor.author | Kingston, Robert E. | ko |
dc.contributor.author | Gusella, James F. | ko |
dc.contributor.author | Conlon, Ronald A. | ko |
dc.contributor.author | MacDonald, Marcy E. | ko |
dc.date.accessioned | 2013-03-09T19:31:34Z | - |
dc.date.available | 2013-03-09T19:31:34Z | - |
dc.date.created | 2012-02-06 | - |
dc.date.created | 2012-02-06 | - |
dc.date.issued | 2010-02 | - |
dc.identifier.citation | HUMAN MOLECULAR GENETICS, v.19, no.4, pp.573 - 583 | - |
dc.identifier.issn | 0964-6906 | - |
dc.identifier.uri | http://hdl.handle.net/10203/97301 | - |
dc.description.abstract | Huntington's disease (HD) is caused by expansion of the polymorphic polyglutamine segment in the huntingtin protein. Full-length huntingtin is thought to be a predominant HEAT repeat alpha-solenoid, implying a role as a facilitator of macromolecular complexes. Here we have investigated huntingtin's domain structure and potential intersection with epigenetic silencer polycomb repressive complex 2 (PRC2), suggested by shared embryonic deficiency phenotypes. Analysis of a set of full-length recombinant huntingtins, with different polyglutamine regions, demonstrated dramatic conformational flexibility, with an accessible hinge separating two large alpha-helical domains. Moreover, embryos lacking huntingtin exhibited impaired PRC2 regulation of Hox gene expression, trophoblast giant cell differentiation, paternal X chromosome inactivation and histone H3K27 tri-methylation, while full-length endogenous nuclear huntingtin in wild-type embryoid bodies (EBs) was associated with PRC2 subunits and was detected with trimethylated histone H3K27 at Hoxb9. Supporting a direct stimulatory role, full-length recombinant huntingtin significantly increased the histone H3K27 tri-methylase activity of reconstituted PRC2 in vitro, and structure-function analysis demonstrated that the polyglutamine region augmented full-length huntingtin PRC2 stimulation, both in Hdh(Q111) EBs and in vitro, with reconstituted PRC2. Knowledge of full-length huntingtin's alpha-helical organization and role as a facilitator of the multi-subunit PRC2 complex provides a novel starting point for studying PRC2 regulation, implicates this chromatin repressive complex in a neurodegenerative disorder and sets the stage for further study of huntingtin's molecular function and the impact of its modulatory polyglutamine region. | - |
dc.language | English | - |
dc.publisher | OXFORD UNIV PRESS | - |
dc.subject | HISTONE METHYLTRANSFERASE ACTIVITY | - |
dc.subject | DISEASE GENE HOMOLOG | - |
dc.subject | SECONDARY STRUCTURE | - |
dc.subject | IN-VIVO | - |
dc.subject | EMBRYONIC LETHALITY | - |
dc.subject | MOUSE DEVELOPMENT | - |
dc.subject | PROTEIN-SEQUENCE | - |
dc.subject | IMPORTIN-BETA | - |
dc.subject | REPEAT | - |
dc.subject | POLYGLUTAMINE | - |
dc.title | Huntingtin facilitates polycomb repressive complex 2 | - |
dc.type | Article | - |
dc.identifier.wosid | 000273702200002 | - |
dc.identifier.scopusid | 2-s2.0-77949774027 | - |
dc.type.rims | ART | - |
dc.citation.volume | 19 | - |
dc.citation.issue | 4 | - |
dc.citation.beginningpage | 573 | - |
dc.citation.endingpage | 583 | - |
dc.citation.publicationname | HUMAN MOLECULAR GENETICS | - |
dc.identifier.doi | 10.1093/hmg/ddp524 | - |
dc.contributor.localauthor | Song, Ji-Joon | - |
dc.contributor.nonIdAuthor | Seong, Ihn Sik | - |
dc.contributor.nonIdAuthor | Woda, Juliana M. | - |
dc.contributor.nonIdAuthor | Lloret, Alejandro | - |
dc.contributor.nonIdAuthor | Abeyrathne, Priyanka D. | - |
dc.contributor.nonIdAuthor | Woo, Caroline J. | - |
dc.contributor.nonIdAuthor | Gregory, Gillian | - |
dc.contributor.nonIdAuthor | Lee, Jong-Min | - |
dc.contributor.nonIdAuthor | Wheeler, Vanessa C. | - |
dc.contributor.nonIdAuthor | Walz, Thomas | - |
dc.contributor.nonIdAuthor | Kingston, Robert E. | - |
dc.contributor.nonIdAuthor | Gusella, James F. | - |
dc.contributor.nonIdAuthor | Conlon, Ronald A. | - |
dc.contributor.nonIdAuthor | MacDonald, Marcy E. | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | HISTONE METHYLTRANSFERASE ACTIVITY | - |
dc.subject.keywordPlus | DISEASE GENE HOMOLOG | - |
dc.subject.keywordPlus | SECONDARY STRUCTURE | - |
dc.subject.keywordPlus | IN-VIVO | - |
dc.subject.keywordPlus | EMBRYONIC LETHALITY | - |
dc.subject.keywordPlus | MOUSE DEVELOPMENT | - |
dc.subject.keywordPlus | PROTEIN-SEQUENCE | - |
dc.subject.keywordPlus | IMPORTIN-BETA | - |
dc.subject.keywordPlus | REPEAT | - |
dc.subject.keywordPlus | POLYGLUTAMINE | - |
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