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

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Publication date 2011
Author Meylan Sylvain, Groner Anna C, Ambrosini Giovanna, Malani Nirav, Quenneville Simon, Zangger Nadine, Kapopoulou Adamandia, Kauzlaric Annamaria, Rougemont Jacques, Ciuffi Angela, Bushman Frederic D, Bucher Philipp, Trono Didier,
Project KRAB/KAP1 epigenetic regulation in the control of memory and emotional traits: from mice to humans.
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Original article (peer-reviewed)

Journal BMC genomics
Volume (Issue) 12
Page(s) 378 - 378
Title of proceedings BMC genomics
DOI 10.1186/1471-2164-12-378

Abstract

BACKGROUND 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.
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