DREAM represses distinct targets by cooperating with different THAP domain proteins.
Accepted version
Peer-reviewed
Repository URI
Repository DOI
Change log
Authors
Abstract
The DREAM (dimerization partner [DP], retinoblastoma [Rb]-like, E2F, and MuvB) complex controls cellular quiescence by repressing cell-cycle and other genes, but its mechanism of action is unclear. Here, we demonstrate that two C. elegans THAP domain proteins, LIN-15B and LIN-36, co-localize with DREAM and function by different mechanisms for repression of distinct sets of targets. LIN-36 represses classical cell-cycle targets by promoting DREAM binding and gene body enrichment of H2A.Z, and we find that DREAM subunit EFL-1/E2F is specific for LIN-36 targets. In contrast, LIN-15B represses germline-specific targets in the soma by facilitating H3K9me2 promoter marking. We further find that LIN-36 and LIN-15B differently regulate DREAM binding. In humans, THAP proteins have been implicated in cell-cycle regulation by poorly understood mechanisms. We propose that THAP domain proteins are key mediators of Rb/DREAM function.
Description
Keywords
Journal Title
Conference Name
Journal ISSN
2211-1247
Volume Title
Publisher
Publisher DOI
Rights
Sponsorship
Wellcome Trust (101863/Z/13/Z)
Cancer Research Uk (None)
MRC (MR/S021620/1)