DREAM represses distinct targets by cooperating with different THAP domain proteins

• Published in: Cell reports (Cambridge) 2021-10, Vol.37 (3), p.109835-109835, Article 109835
• Main Authors: Gal, Csenge, Carelli, Francesco Nicola, Appert, Alex, Cerrato, Chiara, Huang, Ni, Dong, Yan, Murphy, Jane, Frapporti, Andrea, Ahringer, Julie
• Format: Article
• Language: English
• Subjects: Animals; Animals, Genetically Modified; Caenorhabditis elegans - genetics; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; DNA Methylation; DREAM; E2F Transcription Factors - genetics; E2F Transcription Factors - metabolism; Gene Expression Regulation; H2A.Z; H3K9me2; Histones - genetics; Histones - metabolism; lin-15B; lin-35; lin-36; Promoter Regions, Genetic; Protein Binding; Protein Interaction Domains and Motifs; quiescence; retinoblastoma; Retinoblastoma Protein - genetics; Retinoblastoma Protein - metabolism; THAP; Transcription Factors - genetics; Transcription Factors - metabolism; transcriptional repression
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2021.109835

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. [Display omitted] •THAP domain proteins LIN-36 and LIN-15B cooperate with the Rb-DREAM complex•LIN-36 and LIN-15B repress distinct sets of DREAM targets via different mechanisms•With LIN-36, DREAM represses cell-cycle genes through gene body enrichment of H2A.Z•With LIN-15B, DREAM represses germline genes through H3K9me2 promoter marking Gal et al. show that two THAP domain proteins are key mediators of retinoblastoma-DREAM function in C. elegans, repressing distinct targets by different mechanisms. With LIN-36, DREAM represses cell-cycle genes through gene body enrichment of H2A.Z; with LIN-15B, DREAM represses germline-specific genes in the soma through H3K9me2 promoter marking.