title: Genome-wide distribution of Auts2 binding localizes with active neurodevelopmental genes.
abstract: 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.
authors.affiliation: 1] Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA [2] Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Oksenberg
authors.affiliation: 1] Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA [2] Gladstone Institutes, San Francisco, CA, USA.
authors.forename: G D E
authors.initials: GD
authors.lastname: Haliburton
authors.affiliation: 1] Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA [2] Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA.
authors.forename: W L
authors.initials: WL
authors.lastname: Eckalbar
authors.affiliation: Department of Life Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: I
authors.initials: I
authors.lastname: Oren
authors.affiliation: 1] Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA [2] Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Nishizaki
authors.affiliation: 1] Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA [2] Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Murphy
authors.affiliation: 1] Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA [2] Gladstone Institutes, San Francisco, CA, USA [3] Division of Biostatistics, University of California San Francisco, San Francisco, CA, USA.
authors.forename: K S
authors.initials: KS
authors.lastname: Pollard
authors.affiliation: 1] Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA [2] Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA [3] Department of Life Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: R Y
authors.initials: RY
authors.lastname: Birnbaum
authors.affiliation: 1] Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA [2] Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Ahituv
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins; D002659:Child Development Disorders, Pervasive / Q000235:genetics*; D003598:Cytoskeletal Proteins; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D051379:Mice; D008815:Mice, Inbred Strains; D019006:Neural Cell Adhesion Molecules / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000235:genetics; D011247:Pregnancy; D016548:Prosencephalon / Q000196:embryology; D014157:Transcription Factors / Q000235:genetics; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: C549397:Auts2 protein, mouse; D002135:Calcium-Binding Proteins; D003598:Cytoskeletal Proteins; D019006:Neural Cell Adhesion Molecules; C527193:Nrxn1 protein, mouse; D009687:Nuclear Proteins; D014157:Transcription Factors; D053499:Plasma Membrane Calcium-Transporting ATPases; C506959:Atp2b2 protein, mouse