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KAP1 regulates gene networks controlling mouse B-lymphoid cell differentiation and function.

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Publication date 2012
Author Santoni de Sio Francesca R, Massacand Joanna, Barde Isabelle, Offner Sandra, Corsinotti Andrea, Kapopoulou Adamandia, Bojkowska Karolina, Dagklis Antonis, Fernandez Marylise, Ghia Paolo, Thomas James H, Pinschewer Daniel, Harris Nicola, Trono Didier,
Project Innate defenses against retroelements
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Original article (peer-reviewed)

Journal Blood
Volume (Issue) 119(20)
Page(s) 4675 - 85
Title of proceedings Blood
DOI 10.1182/blood-2011-12-401117


Chromatin remodeling is fundamental for B-cell differentiation. In the present study, we explored the role of KAP1, the cofactor of KRAB-ZFP transcriptional repressors, in this process. B-lymphoid-specific Kap1-KO mice displayed reduced numbers of mature B cells, lower steady-state levels of Abs, and accelerated rates of decay of neutralizing Abs after viral immunization. Transcriptome analyses of Kap1-deleted B splenocytes revealed an up-regulation of PTEN, the enzymatic counteractor of PIK3 signaling, and of genes encoding DNA-damage response factors, cell-cycle regulators, and chemokine receptors. ChIP/seq studies established that KAP1 bound at or close to several of these genes and controlled chromatin status at their promoters. Genome wide, KAP1 binding sites lacked active B cell-specific enhancers and were enriched in repressive histone marks, further supporting a role for this molecule in gene silencing in vivo. Likely responsible for tethering KAP1 to at least some of these targets, a discrete subset of KRAB-ZFPs is enriched in B lymphocytes. Our results therefore reveal the role of KRAB/KAP1-mediated epigenetic regulation in B-cell development and homeostasis.