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

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Version: Final published version
Serval ID
serval:BIB_15B6945F2924
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A gene-rich, transcriptionally active environment and the pre-deposition of repressive marks are predictive of susceptibility to KRAB/KAP1-mediated silencing.
Journal
Bmc Genomics
Author(s)
Meylan S., Groner A.C., Ambrosini G., Malani N., Quenneville S., Zangger N., Kapopoulou A., Kauzlaric A., Rougemont J., Ciuffi A., Bushman F.D., Bucher P., Trono D.
ISSN
1471-2164 (Electronic)
ISSN-L
1471-2164
Publication state
Published
Issued date
07/2011
Peer-reviewed
Oui
Volume
12
Pages
378
Language
english
Abstract
AbstractBACKGROUND: 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.METHOD: 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.RESULTS: 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 genes.CONCLUSION: Together, these data indicate that high levels of gene activity in the genomic environment and the pre-deposition of repressive histone marks within a gene increase its susceptibility to KRAB/KAP1-mediated repression.
Keywords
Chromatin/genetics, Gene Silencing, Genomics, HeLa Cells, Histones/genetics, Humans, Repressor Proteins/metabolism, Transcription, Genetic/genetics
Pubmed
Web of science
Open Access
Yes
Create date
20/02/2012 17:49
Last modification date
20/08/2019 12:44
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