Additional sex combs-like 2 is required for polycomb repressive complex 2 binding at select targets.

Polycomb Group (PcG) proteins are epigenetic repressors of gene expression. The Drosophila Additional sex combs (Asx) gene and its mammalian homologs exhibit PcG function in genetic assays; however, the mechanism by which Asx family proteins mediate gene repression is not well understood. ASXL2, one...

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Autores principales:	Hsiao-Lei Lai, Q Tian Wang
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7fd4de33c20447fea997fc803c06f152
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spelling	oai:doaj.org-article:7fd4de33c20447fea997fc803c06f1522021-11-18T08:56:12ZAdditional sex combs-like 2 is required for polycomb repressive complex 2 binding at select targets.1932-620310.1371/journal.pone.0073983https://doaj.org/article/7fd4de33c20447fea997fc803c06f1522013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24040135/?tool=EBIhttps://doaj.org/toc/1932-6203Polycomb Group (PcG) proteins are epigenetic repressors of gene expression. The Drosophila Additional sex combs (Asx) gene and its mammalian homologs exhibit PcG function in genetic assays; however, the mechanism by which Asx family proteins mediate gene repression is not well understood. ASXL2, one of three mammalian homologs for Asx, is highly expressed in the mammalian heart and is required for the maintenance of cardiac function. We have previously shown that Asxl2 deficiency results in a reduction in the bulk level of histone H3 lysine 27 trimethylation (H3K27me3), a repressive mark generated by the Polycomb Repressive Complex 2 (PRC2). Here we identify several ASXL2 target genes in the heart and investigate the mechanism by which ASXL2 facilitates their repression. We show that the Asxl2-deficient heart is defective in converting H3K27me2 to H3K27me3 and in removing ubiquitin from mono-ubiquitinated histone H2A. ASXL2 and PRC2 interact in the adult heart and co-localize to target promoters. ASXL2 is required for the binding of PRC2 and for the enrichment of H3K27me3 at target promoters. These results add a new perspective to our understanding of the mechanisms that regulate PcG activity and gene repression.Hsiao-Lei LaiQ Tian WangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 9, p e73983 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hsiao-Lei Lai Q Tian Wang Additional sex combs-like 2 is required for polycomb repressive complex 2 binding at select targets.
description	Polycomb Group (PcG) proteins are epigenetic repressors of gene expression. The Drosophila Additional sex combs (Asx) gene and its mammalian homologs exhibit PcG function in genetic assays; however, the mechanism by which Asx family proteins mediate gene repression is not well understood. ASXL2, one of three mammalian homologs for Asx, is highly expressed in the mammalian heart and is required for the maintenance of cardiac function. We have previously shown that Asxl2 deficiency results in a reduction in the bulk level of histone H3 lysine 27 trimethylation (H3K27me3), a repressive mark generated by the Polycomb Repressive Complex 2 (PRC2). Here we identify several ASXL2 target genes in the heart and investigate the mechanism by which ASXL2 facilitates their repression. We show that the Asxl2-deficient heart is defective in converting H3K27me2 to H3K27me3 and in removing ubiquitin from mono-ubiquitinated histone H2A. ASXL2 and PRC2 interact in the adult heart and co-localize to target promoters. ASXL2 is required for the binding of PRC2 and for the enrichment of H3K27me3 at target promoters. These results add a new perspective to our understanding of the mechanisms that regulate PcG activity and gene repression.
format	article
author	Hsiao-Lei Lai Q Tian Wang
author_facet	Hsiao-Lei Lai Q Tian Wang
author_sort	Hsiao-Lei Lai
title	Additional sex combs-like 2 is required for polycomb repressive complex 2 binding at select targets.
title_short	Additional sex combs-like 2 is required for polycomb repressive complex 2 binding at select targets.
title_full	Additional sex combs-like 2 is required for polycomb repressive complex 2 binding at select targets.
title_fullStr	Additional sex combs-like 2 is required for polycomb repressive complex 2 binding at select targets.
title_full_unstemmed	Additional sex combs-like 2 is required for polycomb repressive complex 2 binding at select targets.
title_sort	additional sex combs-like 2 is required for polycomb repressive complex 2 binding at select targets.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/7fd4de33c20447fea997fc803c06f152
work_keys_str_mv	AT hsiaoleilai additionalsexcombslike2isrequiredforpolycombrepressivecomplex2bindingatselecttargets AT qtianwang additionalsexcombslike2isrequiredforpolycombrepressivecomplex2bindingatselecttargets
_version_	1718421149223747584

Additional sex combs-like 2 is required for polycomb repressive complex 2 binding at select targets.

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