The KAT module of the SAGA complex maintains the oncogenic gene expression program in <i>MYCN-</i>amplified neuroblastoma.

ABSTRACT: Pediatric cancers are frequently driven by genomic alterations that result in aberrant transcription factor activity. Here, we used functional genomic screens to identify multiple genes within the transcriptional coactivator Spt-Ada-Gcn5-acetyltransferase (SAGA) complex as selective dependencies for MYCN-amplified neuroblastoma, a disease of dysregulated development driven by an aberrant oncogenic transcriptional program. We characterized the DNA recruitment sites of the SAGA complex in neuroblastoma and the consequences of loss of SAGA complex lysine acetyltransferase (KAT) activity on histone acetylation and gene expression. We demonstrate that loss of SAGA complex KAT activity is associated with reduced MYCN binding on chromatin, suppression of MYC/MYCN gene expression programs,

SUBMITTER: Malone CF 

PROVIDER: S-EPMC11141635 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature