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

ABSTRACT: A multilayered transcription regulatory system is unveiled, where protein- and RNA-based repressors are super-imposed in combinatorial fashion to govern the timely triggering of an essential step of erythropoiesis Analyses of transcriptional profiles and chromatin state in KAP1 WT and KO cells

ORGANISM(S): Mus musculus

SUBMITTER: Adamandia Kapopoulou

PROVIDER: E-GEOD-44063 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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A KRAB/KAP1-miRNA cascade regulates erythropoiesis through stage-specific control of mitophagy.

Barde Isabelle I Rauwel Benjamin B Marin-Florez Ray Marcel RM Corsinotti Andrea A Laurenti Elisa E Verp Sonia S Offner Sandra S Marquis Julien J Kapopoulou Adamandia A Vanicek Jiri J Trono Didier D

Science (New York, N.Y.) 20130314 6130

During hematopoiesis, lineage- and stage-specific transcription factors work in concert with chromatin modifiers to direct the differentiation of all blood cells. We explored the role of KRAB-containing zinc finger proteins (KRAB-ZFPs) and their cofactor KAP1 in this process. In mice, hematopoietic-restricted deletion of Kap1 resulted in severe hypoproliferative anemia. Kap1-deleted erythroblasts failed to induce mitophagy-associated genes and retained mitochondria. This was due to persistent ex ...[more]

PMID: 23493425

Similar Datasets

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

2013-04-03 | E-GEOD-44065 | biostudies-arrayexpress

Gene expression analysis of wild type and KAP1 KO splenic B cells

Project description:Chromatin remodeling is fundamental for B cell differentiation. Here, we explored the role in this process of KAP1, the cofactor of KRAB-ZFP transcriptional repressors. B lymphoid-specific Kap1 knockout mice displayed reduced numbers of mature B cells, lower steady-state levels of antibodies and accelerated rates of decay of neutralizing antibodies following viral immunization. Transcriptome analyses of Kap1-deleted B splenocytes revealed an upregulation of PTEN, the enzymatic counter-actor 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 a number of these genes, and controlled chromatin status at their promoters. Genome-wide, KAP1-binding sites avoided 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. This work thus reveals the role of KRAB/KAP1-mediated epigenetic regulation in B cell development and homeostasis. Follicular (FO) and Transcriptional 2 Follicular Progenitor (T2-FP) B cells were sorted out from 3 CD19-Cre/Kap1flox (KAP1 KO in the B lineage) mice and 3 wt/Kap1flox littermate controls

2012-05-16 | E-GEOD-34446 | biostudies-arrayexpress

Gene expression analysis of wild type and KAP1 KO mouse T cell progenitors

Project description:The modulation of chromatin status at specific genomic loci controls lymphoid differentiation. Here, we investigated the role played in this process by KAP1, the universal cofactor of KRAB-containing Zinc Finger Proteins (KRAB-ZFPs), a tetrapod-restricted family of transcriptional repressors. T cell-specific Kap1 knockout mice displayed a significant expansion of immature thymocytes and imbalances in the ratios of mature T cells in the thymus and the spleen, with impaired responses to TCR stimulation. Transcriptome and chromatin studies revealed that KAP1 directly controls the expression of a number of genes involved in TCR and cytokine signalling, among which Traf1 and FoxO1, and is strongly associated with cis-acting regulatory elements marked by the H3K9me3 repressive mark on the genome of thymic T cells. 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 KRAB/KAP1-mediated epigenetic regulation in T lymphocyte differentiation and activation. Cells were harvested form the thymus of 3 CD4-Cre/Kap1flox (KAP1 KO in the T lineage) mice and 3 wt/Kap1flox littermate controls

2012-12-16 | E-GEOD-34447 | biostudies-arrayexpress

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

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

2012-08-07 | E-GEOD-38580 | biostudies-arrayexpress

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

Project description:A multilayered transcription regulatory system is unveiled, where protein- and RNA-based repressors are super-imposed in combinatorial fashion to govern the timely triggering of an essential step of erythropoiesis Analyses of transcriptional profiles and chromatin state in KAP1 WT and KO (or KD) cells

2013-04-03 | E-GEOD-44061 | biostudies-arrayexpress

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

2013-04-03 | GSE44063 | GEO

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

2013-04-03 | GSE44061 | GEO

A KRAB/KAP1-miRNA cascade regulates erythropoiesis through stage-specific control of mitophagy.

Project description:During hematopoiesis, lineage- and stage-specific transcription factors work in concert with chromatin modifiers to direct the differentiation of all blood cells. We explored the role of KRAB-containing zinc finger proteins (KRAB-ZFPs) and their cofactor KAP1 in this process. In mice, hematopoietic-restricted deletion of Kap1 resulted in severe hypoproliferative anemia. Kap1-deleted erythroblasts failed to induce mitophagy-associated genes and retained mitochondria. This was due to persistent expression of microRNAs (miRNAs) targeting mitophagy transcripts, itself secondary to a lack of repression by stage-specific KRAB-ZFPs. The KRAB/KAP1-miRNA regulatory cascade is evolutionarily conserved, as it also controls mitophagy during human erythropoiesis. Thus, a multilayered transcription regulatory system is present, in which protein- and RNA-based repressors are superimposed in combinatorial fashion to govern the timely triggering of an important differentiation event.

| S-EPMC3678075 | biostudies-literature

PEG3 Interacts with KAP1 through KRAB-A.

Project description:Peg3 (Paternally Expressed Gene 3) is an imprinted gene that encodes a zinc finger DNA-binding protein. Peg3 itself is localized in the middle of a KRAB-A (Kruppel-Associated Box) zinc finger gene cluster. The amino acid sequence encoded by its exon 7 also shows sequence similarity to that of KRAB-A, suggesting Peg3 as a KRAB-containing zinc finger gene. As predicted, the PEG3 protein was co-immunoprecipitated with KAP1, a co-repressor that interacts with KRAB-A. A series of follow-up experiments further demonstrated that the exon 7 of PEG3 is indeed responsible for its physical interaction with KAP1. ChIP and promoter assays also indicated that PEG3 likely controls its downstream genes through the KAP1-mediated repression mechanism. Overall, the current study identifies PEG3 as a KRAB-containing zinc finger protein that interacts with the co-repressor protein KAP1.

| S-EPMC5127583 | biostudies-literature

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