AUTS2 confers gene activation to Polycomb group proteins in the CNS

Naturally occurring variations of Polycomb Repressive Complex 1 (PRC1) comprise a core assembly of Polycomb group proteins and additional factors that include, surprisingly, Autism Susceptibility Candidate 2 (AUTS2). While AUTS2 is often disrupted in patients with neuronal disorders, the underlying...

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Main Authors:	Gao, Zhonghua, Lee, Pedro, Stafford, James M., von Schimmelmann, Melanie, Schaefer, Anne, Reinberg, Danny
Format:	Online
Language:	English
Published:	2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4323097/

id	pubmed-4323097
recordtype	oai_dc
spelling	pubmed-43230972015-06-18 AUTS2 confers gene activation to Polycomb group proteins in the CNS Gao, Zhonghua Lee, Pedro Stafford, James M. von Schimmelmann, Melanie Schaefer, Anne Reinberg, Danny Article Naturally occurring variations of Polycomb Repressive Complex 1 (PRC1) comprise a core assembly of Polycomb group proteins and additional factors that include, surprisingly, Autism Susceptibility Candidate 2 (AUTS2). While AUTS2 is often disrupted in patients with neuronal disorders, the underlying mechanism is unclear. We investigated the role of AUTS2 as part of a previously identified PRC1 complex (PRC1-AUTS2), and in the context of neurodevelopment. In contrast to the canonical role of PRC1 in gene repression, PRC1-AUTS2 activates transcription. Biochemical studies demonstrated that the CK2 component of PRC1-AUTS2 thwarts PRC1 repressive activity while AUTS2-mediated recruitment of P300 leads to gene activation. ChIP-seq demonstrated that AUTS2 regulates neuronal gene expression through promoter association. Conditional targeting of Auts2 in the mouse central nervous system (CNS) leads to various developmental defects. These findings reveal a natural means of subverting PRC1 activity, linking key epigenetic modulators with neuronal functions and diseases. 2014-12-18 /pmc/articles/PMC4323097/ /pubmed/25519132 http://dx.doi.org/10.1038/nature13921 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Gao, Zhonghua Lee, Pedro Stafford, James M. von Schimmelmann, Melanie Schaefer, Anne Reinberg, Danny
spellingShingle	Gao, Zhonghua Lee, Pedro Stafford, James M. von Schimmelmann, Melanie Schaefer, Anne Reinberg, Danny AUTS2 confers gene activation to Polycomb group proteins in the CNS
author_facet	Gao, Zhonghua Lee, Pedro Stafford, James M. von Schimmelmann, Melanie Schaefer, Anne Reinberg, Danny
author_sort	Gao, Zhonghua
title	AUTS2 confers gene activation to Polycomb group proteins in the CNS
title_short	AUTS2 confers gene activation to Polycomb group proteins in the CNS
title_full	AUTS2 confers gene activation to Polycomb group proteins in the CNS
title_fullStr	AUTS2 confers gene activation to Polycomb group proteins in the CNS
title_full_unstemmed	AUTS2 confers gene activation to Polycomb group proteins in the CNS
title_sort	auts2 confers gene activation to polycomb group proteins in the cns
description	Naturally occurring variations of Polycomb Repressive Complex 1 (PRC1) comprise a core assembly of Polycomb group proteins and additional factors that include, surprisingly, Autism Susceptibility Candidate 2 (AUTS2). While AUTS2 is often disrupted in patients with neuronal disorders, the underlying mechanism is unclear. We investigated the role of AUTS2 as part of a previously identified PRC1 complex (PRC1-AUTS2), and in the context of neurodevelopment. In contrast to the canonical role of PRC1 in gene repression, PRC1-AUTS2 activates transcription. Biochemical studies demonstrated that the CK2 component of PRC1-AUTS2 thwarts PRC1 repressive activity while AUTS2-mediated recruitment of P300 leads to gene activation. ChIP-seq demonstrated that AUTS2 regulates neuronal gene expression through promoter association. Conditional targeting of Auts2 in the mouse central nervous system (CNS) leads to various developmental defects. These findings reveal a natural means of subverting PRC1 activity, linking key epigenetic modulators with neuronal functions and diseases.
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4323097/
_version_	1613186309623382016

AUTS2 confers gene activation to Polycomb group proteins in the CNS

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