Project description:This SuperSeries is composed of the following subset Series: GSE34447: Gene expression analysis of wild type and KAP1 KO mouse T cell progenitors GSE38579: ChIP-seq analysis of KAP1 binding and H3K9me3 modifications in mouse T cell progenitors Refer to individual Series
Project description: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 TGF? 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.
Project description:This SuperSeries is composed of the following subset Series: GSE34446: Gene expression analysis of wild type and KAP1 KO splenic B cells GSE36850: ChIP-seq analysis of KAP1 and H3K9me3 modifications in mouse spleen B cells Refer to individual Series