Functional conservation of Asxl2, a murine homolog for the Drosophila enhancer of trithorax and polycomb group gene Asx.

<h4>Background</h4>Polycomb-group (PcG) and trithorax-group (trxG) proteins regulate histone methylation to establish repressive and active chromatin configurations at target loci, respectively. These chromatin configurations are passed on from mother to daughter cells, thereby causing h...

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Autores principales:	Heather A Baskind, Lucy Na, Quanhong Ma, Mayur P Patel, David L Geenen, Q Tian Wang
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/336e6341584b45979286c01af55afd10
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spelling	oai:doaj.org-article:336e6341584b45979286c01af55afd102021-11-25T06:16:51ZFunctional conservation of Asxl2, a murine homolog for the Drosophila enhancer of trithorax and polycomb group gene Asx.1932-620310.1371/journal.pone.0004750https://doaj.org/article/336e6341584b45979286c01af55afd102009-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19270745/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Polycomb-group (PcG) and trithorax-group (trxG) proteins regulate histone methylation to establish repressive and active chromatin configurations at target loci, respectively. These chromatin configurations are passed on from mother to daughter cells, thereby causing heritable changes in gene expression. The activities of PcG and trxG proteins are regulated by a special class of proteins known as Enhancers of trithorax and Polycomb (ETP). The Drosophila gene Additional sex combs (Asx) encodes an ETP protein and mutations in Asx enhance both PcG and trxG mutant phenotypes. The mouse and human genomes each contain three Asx homologues, Asx-like 1, 2, and 3. In order to understand the functions of mammalian Asx-like (Asxl) proteins, we generated an Asxl2 mutant mouse from a gene-trap ES cell line.<h4>Methodology/principal findings</h4>We show that the Asxl2 gene trap is expressed at high levels in specific tissues including the heart, the axial skeleton, the neocortex, the retina, spermatogonia and developing oocytes. The gene trap mutation is partially embryonic lethal and approximately half of homozygous animals die before birth. Homozygotes that survive embryogenesis are significantly smaller than controls and have a shortened life span. Asxl2(-/-) mice display both posterior transformations and anterior transformation in the axial skeleton, suggesting that the loss of Asxl2 disrupts the activities of both PcG and trxG proteins. The PcG-associated histone modification, trimethylation of histone H3 lysine 27, is reduced in Asxl2(-/-) heart. Necropsy and histological analysis show that mutant mice have enlarged hearts and may have impaired heart function.<h4>Conclusions/significance</h4>Our results suggest that murine Asxl2 has conserved ETP function and plays dual roles in the promotion of PcG and trxG activity. We have also revealed an unexpected role for Asxl2 in the heart, suggesting that the PcG/trxG system may be involved in the regulation of cardiac function.Heather A BaskindLucy NaQuanhong MaMayur P PatelDavid L GeenenQ Tian WangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 3, p e4750 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Heather A Baskind Lucy Na Quanhong Ma Mayur P Patel David L Geenen Q Tian Wang Functional conservation of Asxl2, a murine homolog for the Drosophila enhancer of trithorax and polycomb group gene Asx.
description	<h4>Background</h4>Polycomb-group (PcG) and trithorax-group (trxG) proteins regulate histone methylation to establish repressive and active chromatin configurations at target loci, respectively. These chromatin configurations are passed on from mother to daughter cells, thereby causing heritable changes in gene expression. The activities of PcG and trxG proteins are regulated by a special class of proteins known as Enhancers of trithorax and Polycomb (ETP). The Drosophila gene Additional sex combs (Asx) encodes an ETP protein and mutations in Asx enhance both PcG and trxG mutant phenotypes. The mouse and human genomes each contain three Asx homologues, Asx-like 1, 2, and 3. In order to understand the functions of mammalian Asx-like (Asxl) proteins, we generated an Asxl2 mutant mouse from a gene-trap ES cell line.<h4>Methodology/principal findings</h4>We show that the Asxl2 gene trap is expressed at high levels in specific tissues including the heart, the axial skeleton, the neocortex, the retina, spermatogonia and developing oocytes. The gene trap mutation is partially embryonic lethal and approximately half of homozygous animals die before birth. Homozygotes that survive embryogenesis are significantly smaller than controls and have a shortened life span. Asxl2(-/-) mice display both posterior transformations and anterior transformation in the axial skeleton, suggesting that the loss of Asxl2 disrupts the activities of both PcG and trxG proteins. The PcG-associated histone modification, trimethylation of histone H3 lysine 27, is reduced in Asxl2(-/-) heart. Necropsy and histological analysis show that mutant mice have enlarged hearts and may have impaired heart function.<h4>Conclusions/significance</h4>Our results suggest that murine Asxl2 has conserved ETP function and plays dual roles in the promotion of PcG and trxG activity. We have also revealed an unexpected role for Asxl2 in the heart, suggesting that the PcG/trxG system may be involved in the regulation of cardiac function.
format	article
author	Heather A Baskind Lucy Na Quanhong Ma Mayur P Patel David L Geenen Q Tian Wang
author_facet	Heather A Baskind Lucy Na Quanhong Ma Mayur P Patel David L Geenen Q Tian Wang
author_sort	Heather A Baskind
title	Functional conservation of Asxl2, a murine homolog for the Drosophila enhancer of trithorax and polycomb group gene Asx.
title_short	Functional conservation of Asxl2, a murine homolog for the Drosophila enhancer of trithorax and polycomb group gene Asx.
title_full	Functional conservation of Asxl2, a murine homolog for the Drosophila enhancer of trithorax and polycomb group gene Asx.
title_fullStr	Functional conservation of Asxl2, a murine homolog for the Drosophila enhancer of trithorax and polycomb group gene Asx.
title_full_unstemmed	Functional conservation of Asxl2, a murine homolog for the Drosophila enhancer of trithorax and polycomb group gene Asx.
title_sort	functional conservation of asxl2, a murine homolog for the drosophila enhancer of trithorax and polycomb group gene asx.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/336e6341584b45979286c01af55afd10
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Functional conservation of Asxl2, a murine homolog for the Drosophila enhancer of trithorax and polycomb group gene Asx.

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