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HDAC6 deacetylates IDH1 to regulate the homeostasis of hematopoietic stem/progenitor cells [WGBS-seq]

ABSTRACT: HDAC6 deacetylates IDH1 to regulate the homeostasis of hematopoietic stem/progenitor cells [WGBS-seq]

PROVIDER: PRJNA980202 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24829768_1.fastq.gz	Fastqsanger.gz
	SRR24829768_2.fastq.gz	Fastqsanger.gz
	SRR24829769_1.fastq.gz	Fastqsanger.gz
	SRR24829769_2.fastq.gz	Fastqsanger.gz
	SRR24829770_1.fastq.gz	Fastqsanger.gz

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HDAC6 deacetylates IDH1 to regulate the homeostasis of hematopoietic stem/progenitor cells [WGBS-seq]

Project description:In order to further explore the mechanism by which increased 5hmC inhibits expansion of LSK cells from Hdac6-/- murine primary BM cells, we performed WGBS-seq and oxWGBS-seq analysis using LSK cells isolated from Hdac6-/- and WT mice.

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HDAC6 deacetylates IDH1 to regulate the homeostasis of hematopoietic stem/progenitor cells

Project description:HDAC6 deacetylates IDH1 to regulate the homeostasis of hematopoietic stem/progenitor cells

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HDAC6 deacetylates IDH1 to regulate the homeostasis of hematopoietic stem/progenitor cells

Project description:In order to further explore the mechanism by which increased 5hmC inhibits expansion of LSK cells from Hdac6-/- murine primary BM cells, we performed RNA sequencing (RNA-seq) analysis using LSK cells isolated from Hdac6-/- and WT mice.

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HDAC6 deacetylates IDH1 to promote the homeostasis of hematopoietic stem and progenitor cells

Project description:Hematopoietic stem and progenitor cells (HSPCs) are cells mainly present in the bone marrow and capable of forming mature blood cells. However, the epigenetic mechanisms governing the homeostasis of HSPCs remain elusive. Here we demonstrate an important role for histone deacetylase 6 (HDAC6) in regulating this process. Our data show that the percentage of HSPCs in Hdac6 knockout mice is lower than in wild-type mice, due to decreased HSPC proliferation. HDAC6 interacts with isocitrate dehydrogenase 1 (IDH1) and deacetylates IDH1 at lysine 233. The deacetylation of IDH1 inhibits its catalytic activity and thereby decreases the 5-hydroxymethylcytosine level of ten-eleven translocation 2 (TET2) target genes, changing gene expression patterns to promote the proliferation of HSPCs. These findings uncover a role for HDAC6 and IDH1 in regulating the homeostasis of HSPCs and may have implications for the treatment of hematological diseases.

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HDAC6 and HSP90 control the functions of Foxp3+ T regulatory cells

Project description:Foxp3+ T-regulatory cells (Tregs) are key to immune homeostasis such that their diminished numbers or function can cause autoimmunity and allograft rejection. Foxp3+ Tregs express histone/protein deacetylases (HDACs) that regulate chromatin remodeling, gene expression and protein function. Pan-HDAC inhibitors developed for oncology enhance Treg production and suppression but have limited non-oncologic applications given their broad effects. We show, using HDAC6-deficient mice and WT mice treated with HDAC6-specific inhibitors, that HDAC6 inhibition promotes Treg suppressive activity in models of inflammation and autoimmunity, including multiple forms of experimental colitis and fully MHC-incompatible cardiac allograft rejection. Many of the beneficial effects of HDAC6 targeting are also achieved by inhibition of the HDAC6-regulated protein, HSP90. Hence, selective targeting of a single HDAC isoform, HDAC6, or its downstream target, HSP90, can promote Treg-dependent suppression of autoimmunity and transplant rejection. RNA from three independent samples from magnetically separated CD4+CD25+ Treg of HDAC6 knock out, compared to wild type (C57BL6) control

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HDAC6 deacetylates TRIM56 to negatively regulate cGAS-mediated type I interferon response

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HDAC6 and HSP90 control the functions of Foxp3+ T regulatory cells

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