Titre
A gene-rich, transcriptionally active environment and the pre-deposition of repressive marks are predictive of susceptibility to KRAB/KAP1-mediated silencing.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Meylan, S.
Auteure/Auteur
Groner, A.C.
Auteure/Auteur
Ambrosini, G.
Auteure/Auteur
Malani, N.
Auteure/Auteur
Quenneville, S.
Auteure/Auteur
Zangger, N.
Auteure/Auteur
Kapopoulou, A.
Auteure/Auteur
Kauzlaric, A.
Auteure/Auteur
Rougemont, J.
Auteure/Auteur
Ciuffi, A.
Auteure/Auteur
Bushman, F.D.
Auteure/Auteur
Bucher, P.
Auteure/Auteur
Trono, D.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1471-2164
Statut éditorial
Publié
Date de publication
2011-07
Volume
12
Première page
378
Peer-reviewed
Oui
Langue
anglais
Résumé
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.
PID Serval
serval:BIB_15B6945F2924
PMID
Open Access
Oui
Date de création
2012-02-20T16:49:17.001Z
Date de création dans IRIS
2025-05-20T14:42:40Z
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Nom
BIB_15B6945F2924.P001.pdf
Version du manuscrit
published
Taille
627.17 KB
Format
Adobe PDF
PID Serval
serval:BIB_15B6945F2924.P001
URN
urn:nbn:ch:serval-BIB_15B6945F29243
Somme de contrôle
(MD5):19ac609e8676e36d5308e17454f644eb