Genome-wide distribution of Auts2 binding localizes with active neurodevelopmental genes

The autism susceptibility candidate 2 gene (AUTS2) has been associated with multiple neurological diseases including autism spectrum disorders (ASDs). Previous studies showed that AUTS2 has an important neurodevelopmental function and is a suspected master regulator of genes implicated in ASD-relate...

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Main Authors:	Oksenberg, N, Haliburton, G D E, Eckalbar, W L, Oren, I, Nishizaki, S, Murphy, K, Pollard, K S, Birnbaum, R Y, Ahituv, N
Format:	Online
Language:	English
Published:	Nature Publishing Group 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4199417/

id	pubmed-4199417
recordtype	oai_dc
spelling	pubmed-41994172014-10-16 Genome-wide distribution of Auts2 binding localizes with active neurodevelopmental genes Oksenberg, N Haliburton, G D E Eckalbar, W L Oren, I Nishizaki, S Murphy, K Pollard, K S Birnbaum, R Y Ahituv, N Original Article The autism susceptibility candidate 2 gene (AUTS2) has been associated with multiple neurological diseases including autism spectrum disorders (ASDs). Previous studies showed that AUTS2 has an important neurodevelopmental function and is a suspected master regulator of genes implicated in ASD-related pathways. However, the regulatory role and targets of Auts2 are not well known. Here, by using ChIP-seq (chromatin immunoprecipitation followed by deep sequencing) and RNA-seq on mouse embryonic day 16.5 forebrains, we elucidated the gene regulatory networks of Auts2. We find that the majority of promoters bound by Auts2 belong to genes highly expressed in the developing forebrain, suggesting that Auts2 is involved in transcriptional activation. Auts2 non-promoter-bound regions significantly overlap developing brain-associated enhancer marks and are located near genes involved in neurodevelopment. Auts2-marked sequences are enriched for binding site motifs of neurodevelopmental transcription factors, including Pitx3 and TCF3. In addition, we characterized two functional brain enhancers marked by Auts2 near NRXN1 and ATP2B2, both ASD-implicated genes. Our results implicate Auts2 as an active regulator of important neurodevelopmental genes and pathways and identify novel genomic regions that could be associated with ASD and other neurodevelopmental diseases. Nature Publishing Group 2014-09 2014-09-02 /pmc/articles/PMC4199417/ /pubmed/25180570 http://dx.doi.org/10.1038/tp.2014.78 Text en Copyright © 2014 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
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	Oksenberg, N Haliburton, G D E Eckalbar, W L Oren, I Nishizaki, S Murphy, K Pollard, K S Birnbaum, R Y Ahituv, N
spellingShingle	Oksenberg, N Haliburton, G D E Eckalbar, W L Oren, I Nishizaki, S Murphy, K Pollard, K S Birnbaum, R Y Ahituv, N Genome-wide distribution of Auts2 binding localizes with active neurodevelopmental genes
author_facet	Oksenberg, N Haliburton, G D E Eckalbar, W L Oren, I Nishizaki, S Murphy, K Pollard, K S Birnbaum, R Y Ahituv, N
author_sort	Oksenberg, N
title	Genome-wide distribution of Auts2 binding localizes with active neurodevelopmental genes
title_short	Genome-wide distribution of Auts2 binding localizes with active neurodevelopmental genes
title_full	Genome-wide distribution of Auts2 binding localizes with active neurodevelopmental genes
title_fullStr	Genome-wide distribution of Auts2 binding localizes with active neurodevelopmental genes
title_full_unstemmed	Genome-wide distribution of Auts2 binding localizes with active neurodevelopmental genes
title_sort	genome-wide distribution of auts2 binding localizes with active neurodevelopmental genes
description	The autism susceptibility candidate 2 gene (AUTS2) has been associated with multiple neurological diseases including autism spectrum disorders (ASDs). Previous studies showed that AUTS2 has an important neurodevelopmental function and is a suspected master regulator of genes implicated in ASD-related pathways. However, the regulatory role and targets of Auts2 are not well known. Here, by using ChIP-seq (chromatin immunoprecipitation followed by deep sequencing) and RNA-seq on mouse embryonic day 16.5 forebrains, we elucidated the gene regulatory networks of Auts2. We find that the majority of promoters bound by Auts2 belong to genes highly expressed in the developing forebrain, suggesting that Auts2 is involved in transcriptional activation. Auts2 non-promoter-bound regions significantly overlap developing brain-associated enhancer marks and are located near genes involved in neurodevelopment. Auts2-marked sequences are enriched for binding site motifs of neurodevelopmental transcription factors, including Pitx3 and TCF3. In addition, we characterized two functional brain enhancers marked by Auts2 near NRXN1 and ATP2B2, both ASD-implicated genes. Our results implicate Auts2 as an active regulator of important neurodevelopmental genes and pathways and identify novel genomic regions that could be associated with ASD and other neurodevelopmental diseases.
publisher	Nature Publishing Group
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4199417/
_version_	1613145568589119488

Genome-wide distribution of Auts2 binding localizes with active neurodevelopmental genes

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