A CHD8-TRRAP axis facilitates MYC and E2F target gene regulation in human neural stem cells. [ChIP-seq]

Mutations in ATP-dependent chromatin remodeler CHD8 cause one of the most frequent monogenetic forms of autism and is associated with brain overgrowth. Nevertheless, the activities of CHD8 in autism-relevant cell types are still poorly understood. Here, we purify the CHD8 protein from human neural stem cells and determine its interaction partners using mass spectrometry. We identify the TRRAP complex, a coactivator of MYC and E2F transcription factors, as a prominent CHD8 interaction partner. CHD8 colocalizes genome-wide with TRRAP and bind together at MYC and E2F target gene promoters in human neural stem cells. Depletion of CHD8 or TRRAP in human neural stem cells shows downregulation of MYC and E2F target genes as the most prominent gene-regulatory events. MYC and E2F transcription factors are established oncogenes known to regulate cell growth. Our results link CHD8 to TRRAP and suggest they act together in facilitating the regulation of MYC and E2F target genes in neural stem cells. Overall design: Genome binding/occupancy profiling of CHD8 and TRRAP in human neural stem cells by high throughput sequencing.