A gene-rich, transcriptionally active environment and the pre-deposition of repressive marks are predictive of susceptibility to KRAB/KAP1-mediated silencing

BMC Genomics
Sylvain MeylanDidier Trono

Abstract

KRAB-ZFPs (Krüppel-associated box domain-zinc finger proteins) are vertebrate-restricted transcriptional repressors encoded in the hundreds by the mouse and human genomes. They act via an essential cofactor, KAP1, which recruits effectors responsible for the formation of facultative heterochromatin. We have recently shown that KRAB/KAP1 can mediate long-range transcriptional repression through heterochromatin spreading, but also demonstrated that this process is at times countered by endogenous influences. To investigate this issue further we used an ectopic KRAB-based repressor. This system allowed us to tether KRAB/KAP1 to hundreds of euchromatic sites within genes, and to record its impact on gene expression. We then correlated this KRAB/KAP1-mediated transcriptional effect to pre-existing genomic and chromatin structures to identify specific characteristics making a gene susceptible to repression. We found that genes that were susceptible to KRAB/KAP1-mediated silencing carried higher levels of repressive histone marks both at the promoter and over the transcribed region than genes that were insensitive. In parallel, we found a high enrichment in euchromatic marks within both the close and more distant environment of these ...Continue Reading

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Citations

May 19, 2012·The Journal of Biological Chemistry·Anna C GronerDidier Trono
Aug 23, 2012·PloS One·Alexander E Vinogradov
Oct 24, 2012·Proceedings of the National Academy of Sciences of the United States of America·Xianghong LiNancy L Craig
Jan 29, 2013·Trends in Biochemical Sciences·Yiwei LiuXiaodong Cheng
Sep 24, 2015·Annual Review of Cell and Developmental Biology·Marc Friedli, Didier Trono
Jun 12, 2013·Gene·Alexander E Vinogradov
Jan 26, 2013·Journal of Virological Methods·Troy BradyFrederic D Bushman
Aug 9, 2012·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Francesca R Santoni de SioDidier Trono
Jan 31, 2021·Scientific Reports·Amina Ait-AmmarOlivier Rohr

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Methods Mentioned

BETA
immunoprecipitation
gene trapping
gene trap
PCR
gene traps
flow cytometry
ChIP
ChIPseq
Fluorescence activated cell sorting
ChIP-seq

Software Mentioned

REP
FetchGWI
TrapSil
Illumina Pipeline
R environment for statistical computing / graphics
ChIPcor
LV
SDS
RNA Robust Multichip Average
MLV

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