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

BMC Genomics

Research Article

Nirav Malani¹  Frederic D Bushman¹  Angela Ciuffi²  Jacques Rougemont³  Anna C Groner⁴  Simon Quenneville⁴  Sylvain Meylan⁴  Nadine Zangger⁴  Annamaria Kauzlaric⁴  Didier Trono⁴  Adamandia Kapopoulou⁴  Philipp Bucher⁵  Giovanna Ambrosini⁵ 

[1] Department of Microbiology, School of Medicine, University of Pennsylvania, Philadelphia, PA, USA;Institut de Microbiologie, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland;School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland;School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland;Frontiers-in-Genetics National Center of Competence in Research, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland;School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland;Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland;

关键词: KAP1;    KRAB-zinc finger proteins;    transcriptional repression;    chromatin;    heterochromatin;    histone modifications;   

DOI  :  10.1186/1471-2164-12-378

 received in 2011-04-12, accepted in 2011-07-26,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundKRAB-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.MethodTo 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.ResultsWe 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.ConclusionTogether, 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.

【 授权许可】

Unknown   
© Meylan et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.