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Single cell RNA sequencing of primary-isolated erythroid progenitors [BFUE, CFUE, intermediates]

ABSTRACT: Single cell RNA sequencing of primary-isolated erythroid progenitors [BFUE, CFUE, intermediates]

PROVIDER: PRJNA481512 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7531240_1.fastq.gz	Fastqsanger.gz
	SRR7531240_2.fastq.gz	Fastqsanger.gz
	SRR7531250_1.fastq.gz	Fastqsanger.gz
	SRR7531250_2.fastq.gz	Fastqsanger.gz
	SRR7531260_1.fastq.gz	Fastqsanger.gz

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Expression analysis of ZBP-89 deficient human primary erythroid progenitors

Project description:The molecular mechanisms underlying erythroid-specific gene regulation remain incompletely understood. Closely spaced binding sites for GATA, NF-E2/maf and CACCC interacting transcription factors play functionally important roles in globin and other erythroid-specific gene expression. We and others recently identified the CACCC-binding transcription factor ZBP-89 as a novel GATA-1 and NF-E2/mafK interacting partner. Here, we examined the role of ZBP-89 in human globin gene regulation and erythroid maturation using a primary CD34+ cell ex vivo differentiation system. We show that ZBP-89 protein levels rise dramatically during human erythroid differentiation, and that ZBP-89 occupies key cis-regulatory elements within the globin and other erythroid gene loci. ZBP-89 binding correlates strongly with RNA Pol II occupancy, active histone marks, and high-level gene expression. ZBP-89 physically associates with the histone acetyltransferases (HATs) p300 and Gcn5/Trrap, and occupies common sites with Gcn5 within the human globin loci. Lentiviral shRNA knockdown of ZBP-89 results in reduced Gcn5 occupancy, decreased acetylated histone 3 levels, lower globin and erythroid-specific gene expression, and impaired erythroid maturation. Addition of the HDAC inhibitor valproic acid partially reverses the reduced globin gene expression. These findings reveal an activating role for ZBP-89 in human globin gene regulation and erythroid differentiation. Keywords: Human primary erythroid progenitors Expression data of human erythroid progenitors transduced with lentivirus expressing short hairpins against ZBP-89 and control empty vector

2011-08-01 | E-GEOD-31092 | biostudies-arrayexpress