| First Author | Santoni de Sio FR | Year | 2012 |
| Journal | Blood | Volume | 119 |
| Issue | 20 | Pages | 4675-85 |
| PubMed ID | 22452978 | Mgi Jnum | J:330498 |
| Mgi Id | MGI:6840108 | Doi | 10.1182/blood-2011-12-401117 |
| Citation | Santoni de Sio FR, et al. (2012) KAP1 regulates gene networks controlling mouse B-lymphoid cell differentiation and function. Blood 119(20):4675-85 |
| abstractText | 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. |
