Cell reports (Cambridge), 2021-10-19, Vol.37 (3), p.109835-109835
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.
•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.
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
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