KAP1 regulates gene networks controlling T-cell development and responsiveness.

Détails

ID Serval
serval:BIB_84EB5469EE09
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
KAP1 regulates gene networks controlling T-cell development and responsiveness.
Périodique
FASEB Journal
Auteur(s)
Santoni de Sio F.R., Barde I., Offner S., Kapopoulou A., Corsinotti A., Bojkowska K., Genolet R., Thomas J.H., Luescher I.F., Pinschewer D., Harris N., Trono D.
ISSN
1530-6860 (Electronic)
ISSN-L
0892-6638
Statut éditorial
Publié
Date de publication
2012
Volume
26
Numéro
11
Pages
4561-4575
Langue
anglais
Résumé
Chromatin remodeling at specific genomic loci controls lymphoid differentiation. Here, we investigated the role played in this process by Kruppel-associated box (KRAB)-associated protein 1 (KAP1), the universal cofactor of KRAB-zinc finger proteins (ZFPs), a tetrapod-restricted family of transcriptional repressors. T-cell-specific Kap1-deleted mice displayed a significant expansion of immature thymocytes, imbalances in CD4(+)/CD8(+) cell ratios, and altered responses to TCR and TGFβ stimulation when compared to littermate KAP1 control mice. Transcriptome and chromatin studies revealed that KAP1 binds T-cell-specific cis-acting regulatory elements marked by the H3K9me3 repressive mark and enriched in Ikaros/NuRD complexes. Also, KAP1 directly controls the expression of several genes involved in TCR and cytokine signaling. Among these, regulation of FoxO1 seems to play a major role in this system. Likely responsible for tethering KAP1 to at least part of its genomic targets, a small number of KRAB-ZFPs are selectively expressed in T-lymphoid cells. These results reveal the so far unsuspected yet important role of KAP1-mediated epigenetic regulation in T-lymphocyte differentiation and activation.
Pubmed
Web of science
Création de la notice
06/12/2012 19:38
Dernière modification de la notice
03/03/2018 18:55
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