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Genome-wide maps of chromatin state in unstimulated HoxER-PU.1 WT and HoxER-PU.1 KO neutrophils

ABSTRACT: Genome-wide maps of chromatin state in unstimulated HoxER-PU.1 WT and HoxER-PU.1 KO neutrophils

PROVIDER: PRJNA434712 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6751042.fastq.gz	Fastqsanger.gz
	SRR6751043.fastq.gz	Fastqsanger.gz
	SRR6751044.fastq.gz	Fastqsanger.gz
	SRR6751045.fastq.gz	Fastqsanger.gz
	SRR6751046.fastq.gz	Fastqsanger.gz

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Genome-wide maps of chromatin state in unstimulated HoxER-PU.1 WT and HoxER-PU.1 KO neutrophils

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Whole transcriptome profiling of neutrophils (Gr1+) flow-sorted from the BM of PU.1 WT and PU.1 KO mice

Project description:Neutrophils are essential first line defense cells against invading pathogens, yet their inappropriate activation contributes to immunological diseases and can cause collateral tissue damage. However, if and how neutrophils cell-intrinsically titrate their inflammatory response remains unknown. Here, we conditionally deleted PU.1, a key myeloid transcription factor, from the neutrophils of mice undergoing fungal infection, and then performed comprehensive epigenomic profiling. We find that a major function of PU.1 is to restrain the neutrophils’ immune response by broadly suppressing genomic enhancer outputs via recruiting histone deacetylase activity, thereby limiting the immune-stimulatory AP1-transcription factor JUNB from entering chromatin. Thus, neutrophils rely on a direct PU.1 repressor function as rheostat of the inflammatory chromatin state, safeguarding their epigenome from undergoing uncontrolled activation prior to pathogenic stimulation. We performed whole transcriptome profiling of neutrophils (Gr1+) flow-sorted from the BM of PU.1 WT and PU.1 KO mice, and found nearly 1000 differentially expressed transcripts, 443 of which were decreased and 555 increased in PU.1-deleted neutrophils. Functional annotations of the differentially expressed transcripts revealed that differentiation-associated gene sets were not significantly changed in the neutrophils from PU.1∆Neu mice. In contrast, the top ranked gene ontology (GO) sets downregulated in PU.1∆Neu neutrophils represented immunological terms such as inflammatory response, NFκB activity and Toll-like receptor (TLR) signalling.

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