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Induction of OCT2 contributes to regulate the gene expression program in human neutrophils activated via TLR8
- Source :
- Cell Reports, Vol 35, Iss 7, Pp 109143-(2021)
- Publication Year :
- 2021
- Publisher :
- Elsevier, 2021.
-
Abstract
- Summary: The transcription factors (TFs) that regulate inducible genes in activated neutrophils are not yet completely characterized. Herein, we show that the genomic distribution of the histone modification H3K27Ac, as well as PU.1 and C/EBPβ, two myeloid-lineage-determining TFs (LDTFs), significantly changes in human neutrophils treated with R848, a ligand of Toll-like receptor 8 (TLR8). Interestingly, differentially acetylated and LDTF-marked regions reveal an over-representation of OCT-binding motifs that are selectively bound by OCT2/POU2F2. Analysis of OCT2 genomic distribution in primary neutrophils and of OCT2-depletion in HL-60-differentiated neutrophils proves the requirement for OCT2 in contributing to promote, along with nuclear factor κB (NF-κB) and activator protein 1 (AP-1), the TLR8-induced gene expression program in neutrophils. Altogether, our data demonstrate that neutrophils, upon activation via TLR8, profoundly reprogram their chromatin status, ultimately displaying cell-specific, prolonged transcriptome changes. Data also show an unexpected role for OCT2 in amplifying the transcriptional response to TLR8-mediated activation.
- Subjects :
- 0301 basic medicine
Transcription Factor
QH301-705.5
neutrophil, Transcription Factor, OCT2, PU.1, C/EBPβ, TLR8, H3K27Ac
H3K27Ac
OCT2
Neutrophil Activation
General Biochemistry, Genetics and Molecular Biology
Transcriptome
03 medical and health sciences
0302 clinical medicine
Gene expression
Humans
Biology (General)
Receptor
Gene
Transcription factor
TLR8
biology
Chemistry
Gene Expression Profiling
PU.1
Organic Cation Transporter 2
neutrophil
Chromatin
Cell biology
030104 developmental biology
Histone
Toll-Like Receptor 8
C/EBPβ
biology.protein
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 22111247
- Volume :
- 35
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- Cell Reports
- Accession number :
- edsair.doi.dedup.....7442c804bb2106f83ce96503202935a6