| Summary: | 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.
|
|---|