Loss of the Caenorhabditis elegans pocket protein LIN-35 reveals MuvB's innate function as the repressor of DREAM target genes

PLoS Genetics
Paul D GoetschSusan Strome

Abstract

The DREAM (Dp/Retinoblastoma(Rb)-like/E2F/MuvB) transcriptional repressor complex acts as a gatekeeper of the mammalian cell cycle by establishing and maintaining cellular quiescence. How DREAM's three functional components, the E2F-DP heterodimer, the Rb-like pocket protein, and the MuvB subcomplex, form and function at target gene promoters remains unknown. The current model invokes that the pocket protein links E2F-DP and MuvB and is essential for gene repression. We tested this model by assessing how the conserved yet less redundant DREAM system in Caenorhabditis elegans is affected by absence of the sole C. elegans pocket protein LIN-35. Using a LIN-35 protein null mutant, we analyzed the assembly of E2F-DP and MuvB at promoters that are bound by DREAM and the level of expression of those "DREAM target genes" in embryos. We report that LIN-35 indeed mediates the association of E2F-DP and MuvB, a function that stabilizes DREAM subunit occupancy at target genes. In the absence of LIN-35, the occupancy of E2F-DP and MuvB at most DREAM target genes decreases dramatically and many of those genes become upregulated. The retention of E2F-DP and MuvB at some target gene promoters in lin-35 null embryos allowed us to test their con...Continue Reading

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Citations

Mar 9, 2019·Genetics·Edward T Kipreos, Sander van den Heuvel
Oct 24, 2020·Genome Research·Jacques SerizayJulie Ahringer
Sep 10, 2021·Annual Review of Genetics·Hayley WalstonLarisa Litovchick

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Methods Mentioned

BETA
ChIP-seq
immunoprecipitation
co-immunoprecipitation
ChIP
PCR

Software Mentioned

SPP
bowtie
limma
phastCons
DEseq2
affy package
deepTools
DAVID
UCSC genome browser
Bioconductor

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