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KAP1 regulates gene networks controlling B lymphoid cell differentiation and function

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE36880 | GEO | 2012/05/17

SECONDARY ACCESSION(S): PRJNA157145

REPOSITORIES: GEO

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

Project description: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.

| S-EPMC3683646 | biostudies-literature

KAP1 regulates gene networks controlling B lymphoid cell differentiation and function

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

2012-05-16 | E-GEOD-36880 | biostudies-arrayexpress

KAP1 regulates gene networks controlling T cell development and activation

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A KAP1 phosphorylation switch controls MyoD function during skeletal muscle differentiation

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KAP1 regulates gene networks controlling T cell development and activation

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

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

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.

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KRAB/KAP1-microRNA cascade regulates erythropoiesis through the stage-specific control of mitophagy

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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The ubiquitin ligase HUWE1 regulates hematopoietic stem cell maintenance and lymphoid commitment

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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Interleukin-17D regulates group 3 innate lymphoid cell function through its receptor CD93

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