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Pre-established chromatin interactions mediate acute transcriptional response to Epo

ABSTRACT: Pre-established chromatin interactions mediate acute transcriptional response to Epo

PROVIDER: PRJNA595562 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10690943.fastq.gz	Fastqsanger.gz
	SRR10690944.fastq.gz	Fastqsanger.gz
	SRR10690945.fastq.gz	Fastqsanger.gz
	SRR10690946.fastq.gz	Fastqsanger.gz
	SRR10690947.fastq.gz	Fastqsanger.gz

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Pre-established chromatin interactions mediate acute transcriptional response to Epo [HiChIP]

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Pre-established chromatin interactions mediate acute transcriptional response to Epo [HiChIP]

Project description:Although chromatin architecture has been established in a variety of cell and tissue types, chromatin contacts’ dynamics in response to hormone stimulation has yet to be fully elucidated. Using the unique anemia-inducing strain of the Friend virus (FVA) murine model system, we show that there are transcriptional and epigenetic changes in response to erythropoietin within an invariant chromatin domain organization. There is an acute transcriptional response, as seen by genes with significant differential RNA polymerase II occupancy. Additionally, we find that YY1 is highly dynamic in response to Epo stimulation and these binding locations are not shared with CTCF. Using HiChIP, which combines Hi-C and ChIP methodologies, we identified enhancer-promoter interactions mediated by H3K27ac and YY1, revealing a subset of invariant chromatin loops. Together, these findings offer new insights into Epo-mediated gene regulation through chromatin organization.

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Pre-established chromatin interactions mediate acute transcriptional response to Epo

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Erythroid progenitors stimulated with EPO

Project description:CD34+ progenitors were isolated from the bone marrow of three healthy volunteers. CD34+CD71+CD45RA- were FACS sorted to enrich for erythroid progenitors. The cells were cultured for four hours with or without EPO in combination with LY294002, and harvested for RNA extraction, amplification and expression analysis. A compound treatment design type is where the response to administration of a compound or chemical (including biological compounds such as hormones) is assayed. Compound Based Treatment: EPO Keywords: compound_treatment_design

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Project description:Erythropoietin (EPO) drives erythropoiesis and is secreted mainly by the kidney upon hypoxic or anemic stress. The paucity of EPO production in renal EPO-producing cells (REPs) causes renal anemia, one of the most common complications of chronic nephropathies. Although mitochondrial dysfunction is commonly observed in several renal and hematopoietic disorders, the mechanism by which mitochondrial quality control impacts renal anemia remains elusive. In this study, we showed that FUNDC1, a mitophagy receptor, plays a critical role in EPO-driven erythropoiesis induced by stresses. Mechanistically, EPO production is impaired in REPs in Fundc1-/- mice upon stresses, and the impairment is caused by the accumulation of damaged mitochondria, which consequently leads to the elevation of the reactive oxygen species (ROS) level and triggers inflammatory responses by up-regulating proinflammatory cytokines. These inflammatory factors promote the myofibroblastic transformation of REPs, resulting in the reduction of EPO production. We therefore provide a link between aberrant mitophagy and deficient EPO generation in renal anemia. Our results also suggest that the mitochondrial quality control safeguards REPs under stresses, which may serve as a potential therapeutic strategy for the treatment of renal anemia.

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