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DREAM represses distinct targets by cooperating with different THAP domain proteins

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE155191 | GEO | 2020/08/13

REPOSITORIES: GEO

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DREAM represses distinct targets by cooperating with different THAP domain proteins

Project description:Summary 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. Graphical abstract Highlights • 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.

| S-EPMC8552245 | biostudies-literature

DREAM represses distinct targets by cooperating with different THAP domain proteins [RNA-seq]

Project description: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. Furthermore, the function of DREAM subunit EFL-1/E2F is specific for LIN-36 targets. In contrast, LIN-15B represses a subset of germline targets by facilitating H3K9me2 promoter marking. 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, facilitating repression of distinct sets of targets.

2020-08-13 | GSE155190 | GEO

DREAM represses distinct targets by cooperating with different THAP domain proteins [CHIP-seq]

2020-08-13 | GSE155189 | GEO

DREAM represses distinct targets by cooperating with different THAP domain proteins

Project description:DREAM represses distinct targets by cooperating with different THAP domain proteins

| PRJNA648943 | ENA

DREAM represses distinct targets by cooperating with different THAP domain proteins [CHIP-seq]

Project description:DREAM represses distinct targets by cooperating with different THAP domain proteins [CHIP-seq]

| PRJNA648949 | ENA

DREAM represses distinct targets by cooperating with different THAP domain proteins [RNA-seq]

Project description:DREAM represses distinct targets by cooperating with different THAP domain proteins [RNA-seq]

| PRJNA648950 | ENA

The DREAM complex antagonizes WDR5a and represses the productive elongation of transcription in Arabidopsis

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-06-27 | GSE181489 | GEO

The HDAC-Associated Sin3B Protein Represses DREAM Complex Targets and Cooperates with APC/C to Promote Quiescence.

Project description:The mammalian DREAM complex is responsible for the transcriptional repression of hundreds of cell-cycle-related genes in quiescence. How the DREAM complex recruits chromatin-modifying entities to aid in its repression remains unknown. Using unbiased proteomics analysis, we have uncovered a robust association between the chromatin-associated Sin3B protein and the DREAM complex. We have determined that genetic inactivation of Sin3B results in the de-repression of DREAM target genes during quiescence but is insufficient to allow quiescent cells to resume proliferation. However, inactivation of APC/CCDH1 was sufficient for Sin3B-/- cells, but not parental cells, to re-enter the cell cycle. These studies identify Sin3B as a transcriptional corepressor associated with the DREAM complex in quiescence and reveals a functional cooperation between E2F target repression and APC/CCDH1 in the negative regulation of cell-cycle progression.

| S-EPMC6324198 | biostudies-literature