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PLZF limits enhancer activity during hematopoietic progenitor aging

ABSTRACT: PLZF limits enhancer activity during hematopoietic progenitor aging

PROVIDER: PRJNA510975 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8359380.fastq.gz	Fastqsanger.gz
	SRR8359390.fastq.gz	Fastqsanger.gz
	SRR8359400.fastq.gz	Fastqsanger.gz
	SRR8359410.fastq.gz	Fastqsanger.gz
	SRR8359420.fastq.gz	Fastqsanger.gz

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PLZF limits enhancer activity during hematopoietic progenitor aging

Project description:PLZF (promyelocytic leukemia zinc finger) is a transcription factor acting as a global regulator of hematopoietic commitment. PLZF displays an epigenetic specificity by recruiting chromatin-modifying factors but little is known about its role in remodeling chromatin of cells committed towards a given specific hematopoietic lineage. In murine myeloid progenitors, we decipher a new role for PLZF in restraining active genes and enhancers by targeting acetylated lysine 27 of Histone H3 (H3K27ac). Functional analyses reveal that active enhancers bound by PLZF are involved in biological processes related to metabolism and associated with hematopoietic aging. Comparing the epigenome of young and old myeloid progenitors, we reveal that H3K27ac variation at active enhancers is a hallmark of hematopoietic aging. Taken together, these data suggest that PLZF, associated with active enhancers, appears to restrain their activity as an epigenetic gatekeeper of hematopoietic aging.

2018-12-21 | GSE124190 | GEO

PLZF limits enhancer activity during hematopoietic progenitor aging.

Project description:PLZF (promyelocytic leukemia zinc finger) is a transcription factor acting as a global regulator of hematopoietic commitment. PLZF displays an epigenetic specificity by recruiting chromatin-modifying factors but little is known about its role in remodeling chromatin of cells committed toward a given specific hematopoietic lineage. In murine myeloid progenitors, we decipher a new role for PLZF in restraining active genes and enhancers by targeting acetylated lysine 27 of Histone H3 (H3K27ac). Functional analyses reveal that active enhancers bound by PLZF are involved in biological processes related to metabolism and associated with hematopoietic aging. Comparing the epigenome of young and old myeloid progenitors, we reveal that H3K27ac variation at active enhancers is a hallmark of hematopoietic aging. Taken together, these data suggest that PLZF, associated with active enhancers, appears to restrain their activity as an epigenetic gatekeeper of hematopoietic aging.

| S-EPMC6511862 | biostudies-literature

Rad21-mediated NF-κB signaling limits hematopoietic stem cell self-renewal in aging and inflammation

Project description:MTD project_description Inflammation and decreased stem cell function characterize organism aging, yet the relationship between these factors remains incompletely understood. This study shows that aged hematopoietic stem and progenitor cells exhibit increased ground-stage NF-κB activity, which enhances their responsiveness to undergo differentiation and loss of self-renewal in response to inflammation. The study identifies Rad21/cohesin as a critical mediator of NF-κB signals, by increasing chromatin accessibility of inter-/intra-genic and enhancer regions. Rad21/NF-κB are required for normal differentiation, but limit self-renewal of hematopoietic stem cells (HSCs) during aging and inflammation in an NF-κB dependent manner. HSCs from aged mice fail to downregulate Rad21/cohesin and inflammation/differentiation inducing signals in the resolution phase after acute inflammation. and The inhibition of cohesin/NF-κB is sufficient to revert the hypersensitivity of aged HSPCs to inflammation-induced differentiation. During aging, myeloid-biased HSCs with disrupted and naturally occurring reduced expression of Rad21/cohesin are increasingly selected over lymphoid-biased HSCs. Together, Rad21/cohesin mediated NF-κB signaling limits HSPC function during aging and selects for cohesin deficient HSCs with myeloid skewed differentiation.

2018-11-28 | PXD011537 | Pride

PLZF acts as a regulator of cell-cycle genes, restricting hematopoietic stem cell proliferation and prevents hematopoietic stem cell aging.

Project description:To uncover gene programs that are regulated by PLZF in the early hematopoietic compartment, we performed micro array-based gene expression analysis of wild-type (WT) or PLZF-mutant (Zbtb16lu/lu) KSLs. DNA-microarrays were used to define and compare the transcriptional profiles of KSL cells isolated from Zbtb16lu/lu mice and WT mice (n=4).

2016-06-29 | E-MTAB-3682 | biostudies-arrayexpress

Expression data comparing PLZF+/+, PLZF +/lu, PLZF lu/lu gammadelta NKT cells

Project description:Natural killer (NKT) T cells exhibit tissue distribution, surface phenotype, and functional responses that are strikingly different from those of conventional T cells. The transcription factor PLZF is responsible for most of these properties, as its ectopic expression in conventional T cells is sufficient to confer to them an NKT-like phenotype. The molecular program downstream of PLZF, however, is largely unexplored. Here we report that PLZF regulates the expression of a surprisingly small set of genes, many with known immune functions. This includes several established components of the NKT cell developmental program. Transcriptional program downstream of PLZF in gammadelta NKT cells was analyzed by comparing wt, heterozygous and PLZF-deficient gammadelta NKT cells

2012-11-09 | E-GEOD-42168 | biostudies-arrayexpress

Promoter DNA methylation dynamics of human hematopoietic progenitor cells during differentiation and aging

Project description:Array-based analysis of genome-wide DNA methylation changes in human CD34+ hematopoietic progenitor cells during myeloid differentiation and aging.

2011-03-17 | E-MTAB-487 | biostudies-arrayexpress

Gene expression profiling of mouse HSPCs retrovirally transduced with Plzf

Project description:We have previously found the immortalization of mouse HSPCs retrovirally transuced with Plzf. To investigate the moleular mehcanism of the immortalization, we preliminarily performed comprehensive gene expression profiling of Plzf-transduced KSL and myeloid progenitor-enriched (MP) cells using cDNA microarray analysis.

2017-04-26 | GSE84771 | GEO

Expression data comparing PLZF+/+, PLZF +/lu, PLZF lu/lu gammadelta NKT cells

2012-11-09 | GSE42168 | GEO

Transcription profiling of human U937T:PLZF-RARa Inducible Cells

Project description:The PLZF-RARa fusion oncoprotein is overexpressed in the t(11;17) subtype of acute promyelocytic leukemia. Gene expression microarrays were used to identify genes involved in leukemic transformation. We used microarray to detect gene expression changes induced by the PLZF-RARa fusion oncoprotein in the U937 cell line Experiment Overall Design: The U937T:PLZF-RARa cell line was engineered to express PLZF-RARa upon tetracycline removal. PLZF-RARa was induced for 48hr and RNA was extracted and hybridized to Affymetrix HGU133Plus2.0 Chips

2009-12-05 | E-GEOD-18476 | biostudies-arrayexpress

Aging hematopoietic progenitor/stem cells

Project description:To determine how aging impacts gene expression in hematopoietic stem cells (HSCs), human CD34+ cells from bone marrow (34BM) and mobilized stem cell products (34P38NPBSC) were examined using microarray-based expression profiling. Differential expression changes were confirmed by microarray comparisons of younger and older expanded T-cell populations.

2008-12-01 | GSE13496 | GEO

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