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

ABSTRACT: Mutations in ATP-dependent chromatin remodeler CHD8 cause one of the most frequent monogenetic forms of autism and also associate with brain overgrowth. Nevertheless, 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 by 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 TRRAP and CHD8 bind together to MYC- and E2F-target gene promoters in human neural stem cells. Acute depletion of CHD8 or TRRAP from human neural stem cells shows down-regulation of MYC- and E2F-target genes as most prominent gene-regulatory events. MYC and E2F factors are established oncogenes known to regulate cell growth. Our results link CHD8 to TRRAP in facilitating regulation of MYC- and E2F-target genes in neural stem cells.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Embryonic Stem Cell

SUBMITTER: Jeroen Demmers  

LAB HEAD: Jeroen Demmers

PROVIDER: PXD044582 | Pride | 2025-05-06

REPOSITORIES: Pride