The DREAM complex promotes gene body H2A.Z for target repression

Area of Science:

• Epigenetics and Gene Regulation
• Cell Cycle Control
• Chromatin Biology

Background:

• The DREAM (DP, Retinoblastoma [Rb]-like, E2F, and MuvB) complex is known to regulate cellular quiescence by repressing cell cycle genes.
• The precise molecular mechanism by which the DREAM complex exerts its repressive function remains largely unelucidated.

Purpose of the Study:

• To investigate the role of histone variant H2A.Z (HTZ-1 in C. elegans) in the mechanism of action of the DREAM complex.
• To determine how the DREAM complex influences H2A.Z deposition at its target genes and the functional consequence of this association.

Main Methods:

• Analysis of H2A.Z (HTZ-1) distribution in gene bodies of DREAM targets in wild-type and mutant Caenorhabditis elegans.
• Gene expression analysis of DREAM targets in wild-type, lin-35 (p130/Rb-like), and htz-1/H2A.Z mutant strains.

Main Results:

• DREAM target genes in C. elegans exhibit an unusual enrichment of H2A.Z in their gene bodies.
• Loss of lin-35 function leads to decreased gene body H2A.Z and increased expression of DREAM targets.
• Many DREAM targets are upregulated in htz-1/H2A.Z mutants, supporting a repressive role for gene body H2A.Z.

Conclusions:

• The DREAM complex actively facilitates the deposition of high levels of H2A.Z within the gene bodies of its target genes.
• Gene body H2A.Z, influenced by the DREAM complex, plays a significant role in the repression of target gene expression and the maintenance of cellular quiescence.