DREAM represses distinct targets by cooperating with different THAP domain proteins
View / Open Files
Authors
Gal, Csenge
Carelli, Francesco Nicola
Appert, Alex
Cerrato, Chiara
Huang, Ni
Dong, Yan
Murphy, Jane
Publication Date
2020Publisher
Cold Spring Harbor Laboratory
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Gal, C., Carelli, F. N., Appert, A., Cerrato, C., Huang, N., Dong, Y., Murphy, J., & et al. (2020). DREAM represses distinct targets by cooperating with different THAP domain proteins. https://doi.org/10.1101/2020.08.13.249698
Abstract
<h4>ABSTRACT</h4> 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.
Sponsorship
Wellcome Trust (092096/Z/10/Z)
Cancer Research Uk (None)
Wellcome Trust (101863/Z/13/Z)
Identifiers
External DOI: https://doi.org/10.1101/2020.08.13.249698
This record's URL: https://www.repository.cam.ac.uk/handle/1810/332869
Statistics
Total file downloads (since January 2020). For more information on metrics see the
IRUS guide.