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Autism-associated transcriptional regulators target shared loci proximal to brain-expressed genes

ABSTRACT: Autism-associated transcriptional regulators target shared loci proximal to brain-expressed genes

PROVIDER: PRJNA1046206 | ENA |

REPOSITORIES: ENA

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Autism-associated transcriptional regulators target shared loci proximal to brain-expressed genes

Project description:Many autism spectrum disorder (ASD)-associated genes act as transcriptional regulators (TRs). ChIP-seq was used to identify the regulatory targets of ARID1B, BCL11A, FOXP1, TBR1, and TCF7L2, ASD-associated TRs in the developing human and mouse cortex. These TRs shared substantial overlap in the binding sites, especially within open chromatin. The overlap within a promoter region, 1-2,000bp upstream of transcription start site, was highly predictive of brain expressed genes. This signature was observed at 96 out of 102 ASD-associated genes. In vitro CRISPRi against ARID1B and TBR1 delineated downstream convergent biology in mouse cortical cultures. After eight days, NeuN+ and CALB+ cells were decreased, GFAP+ cells were increased, and transcriptomic signatures correlated with the postmortem brain samples from individuals with ASD. We suggest functional convergence across five ASD-associated TRs leads to shared neurodevelopmental outcomes of haploinsufficient disruption.

2023-12-04 | GSE248876 | GEO

Five autism-associated transcriptional regulators target shared loci proximal to brain-expressed genes.

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