| First Author | Fazel Darbandi S | Year | 2024 |
| Journal | Cell Rep | Volume | 43 |
| Issue | 6 | Pages | 114329 |
| PubMed ID | 38850535 | Mgi Jnum | J:375937 |
| Mgi Id | MGI:7660341 | Doi | 10.1016/j.celrep.2024.114329 |
| Citation | Fazel Darbandi S, et al. (2024) Five autism-associated transcriptional regulators target shared loci proximal to brain-expressed genes. Cell Rep 43(6):114329 |
| abstractText | Many autism spectrum disorder (ASD)-associated genes act as transcriptional regulators (TRs). Chromatin immunoprecipitation sequencing (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, 1-2,000 bp upstream of the transcription start site, was highly predictive of brain-expressed genes. This signature was observed in 96 out of 102 ASD-associated genes. In vitro CRISPRi against ARID1B and TBR1 delineated downstream convergent biology in mouse cortical cultures. After 8 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 that functional convergence across five ASD-associated TRs leads to shared neurodevelopmental outcomes of haploinsufficient disruption. |
