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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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

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

ORGANISM(S): Mus musculus

SUBMITTER: Adamandia Kapopoulou

PROVIDER: E-GEOD-44065 | 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

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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 | E-GEOD-44063 | biostudies-arrayexpress

HIF-1synergizes with glucocorticoids to promote BFU-E progenitor self-renewal

Project description:With the aim of finding small molecules that stimulate erythropoiesis earlier than erythropoietin and that enhance CFU-E production, we studied the mechanism by which glucocorticoids increase CFU-E formation. Using BFU-E and CFU-E progenitors purified by a new technique, we demonstrate that glucocorticoids stimulate the earliest (BFU-E) progenitors to undergo limited self-renewal, which increases formation of CFU-E cells > 20-fold. Interestingly, glucocorticoids induce expression of genes in BFU-E cells that contain promoter regions highly enriched for hypoxia-induced factor 1 alpha (HIF1a) binding sites. This suggests activation of HIF1a may enhance or replace the effect of glucocorticoids on BFU-E self-renewal. Indeed, HIF1a activation by a prolyl hydroxylase inhibitor (PHI) synergizes with glucocorticoids and enhances production of CFU-Es 170-fold. Since PHIs are able to increase erythroblast production at very low concentrations of glucocorticoids, PHI-induced stimulation of BFU-E progenitors thus represents a conceptually new therapeutic window for treating Epo-resistant anemia. RNA-Seq was performed on enriched populations of BFU-E, CFU-E and Ter119+ as well as BFU-E enriched cells treated with Dex and DMOG

2010-12-21 | E-GEOD-26086 | 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

Genome-wide ChIP-Seq reveals a dramatic shift in the binding of the transcription factor erythroid Kruppel-like factor during erythrocyte differentiation

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2013-06-17 | E-GEOD-48020 | biostudies-arrayexpress

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

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2011-06-09 | E-GEOD-25602 | biostudies-arrayexpress

ChIP-seq analysis of KAP1 binding and H3K9me3 modifications in mouse T cell progenitors

Project description:Chromatin remodelling 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 impaired responses to TCR 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 signalling. 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. Examination of KAP1 binding sites and H3K9me3-enriched regions in wild type and KAP1 KO mouse thymocytes.

2012-12-16 | E-GEOD-38579 | biostudies-arrayexpress

Expression data from murine beta thalassemia erythroblasts

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2012-03-31 | E-GEOD-34125 | biostudies-arrayexpress

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

2012-12-19 | E-GEOD-28355 | biostudies-arrayexpress