DREAM represses distinct targets by cooperating with different THAP domain proteins
Published version
Peer-reviewed
Repository URI
Repository DOI
Change log
Authors
Abstract
ABSTRACT
The DREAM (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
3101 Biochemistry and Cell Biology, 31 Biological Sciences, Genetics, 1 Underpinning research, 1.1 Normal biological development and functioning, Generic health relevance
Journal Title
Conference Name
Journal ISSN
Volume Title
Publisher
Cold Spring Harbor Laboratory
Publisher DOI
Sponsorship
Wellcome Trust (092096/Z/10/Z)
Cancer Research Uk (None)
Wellcome Trust (101863/Z/13/Z)
Cancer Research Uk (None)
Wellcome Trust (101863/Z/13/Z)