Pluto Bioinformatics

GSE59688: CBP/P300 Function in Repression as well as Activation Regulated by Adenovirus Small E1A [RNA-seq]

Bulk RNA sequencing

Oncogenic transformation by adenovirus small e1a depends on simultaneous interactions with P300/CBP and RB proteins. To understand why, experiments with structure-based e1a mutants were analyzed with RNA- and ChIP-seq. The results indicate that e1a displaces RBs from E2F activation domains and, by promoting P300 acetylation of RB1 K873/K874, locks them into a repressing conformation that interacts with repressive chromatin modifying enzymes. e1a then delivers these repressing p300-e1a-RB1 complexes to cell genes that have unusually high P300 association with the gene body, enriched in genes of the TGFb-, TNF-, and IL1-signaling pathways. The P300-e1a-RB complex condenses chromatin, dependent on HDAC activity, P300 lysine acetylase activity, the P300 bromodomain, and acetylation of RB K873/K874 and e1a K239, contributing to repression of host genes that would otherwise inhibit cell cycling. The data suggest why e1a must bind P300/CBP as well as RBs for oncogenic transformation and why a trimeric P300-e1a-RB1 complex is required. SOURCE: Arnold Berk (berk@mbi.ucla.edu) - UCLA