How cytokine‐driven changes in chromatin topology are converted into gene regulatory circuits during inflammation still remains unclear. Here, we show that interleukin (IL)‐1α induces acute and widespread changes in chromatin accessibility via th...
http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
https://www.riss.kr/link?id=O112850007
Sinah‐Sophia Weiterer ; Johanna Meier‐Soelch ; Theodore Georgomanolis ; Athanasia Mizi ; Anna Beyerlein ; Hendrik Weiser ; Lilija Brant ; Christin Mayr‐Buro ; Liane Jurida ; Knut Beuerlein ; Helmut Müller ; Axel Weber ; Ulas Tenekeci ; Oliver Dittrich‐Breiholz ; Marek Bartkuhn ; Andrea Nist ; Thorsten Stiewe ; Wilfred FJ IJcken ; Tabea Riedlinger ; M Lienhard Schmitz ; Argyris Papantonis ; Michael Kracht
2020년
-
0261-4189
SCI;SCIE;SCOPUS
학술저널
n/a-n/a [※수록면이 p5 이하이면, Review, Columns, Editor's Note, Abstract 등일 경우가 있습니다.]
0
상세조회0
다운로드다국어 초록 (Multilingual Abstract)
How cytokine‐driven changes in chromatin topology are converted into gene regulatory circuits during inflammation still remains unclear. Here, we show that interleukin (IL)‐1α induces acute and widespread changes in chromatin accessibility via th...
How cytokine‐driven changes in chromatin topology are converted into gene regulatory circuits during inflammation still remains unclear. Here, we show that interleukin (IL)‐1α induces acute and widespread changes in chromatin accessibility via the TAK1 kinase and NF‐κB at regions that are highly enriched for inflammatory disease‐relevant SNPs. Two enhancers in the extended chemokine locus on human chromosome 4 regulate the IL‐1α‐inducible IL8 and CXCL1‐3 genes. Both enhancers engage in dynamic spatial interactions with gene promoters in an IL‐1α/TAK1‐inducible manner. Microdeletions of p65‐binding sites in either of the two enhancers impair NF‐κB recruitment, suppress activation and biallelic transcription of the IL8/CXCL2 genes, and reshuffle higher‐order chromatin interactions as judged by i4C interactome profiles. Notably, these findings support a dominant role of the IL8 “master” enhancer in the regulation of sustained IL‐1α signaling, as well as for IL‐8 and IL‐6 secretion. CRISPR‐guided transactivation of the IL8 locus or cross‐TAD regulation by TNFα‐responsive enhancers in a different model locus supports the existence of complex enhancer hierarchies in response to cytokine stimulation that prime and orchestrate proinflammatory chromatin responses downstream of NF‐κB.
ATAC‐seq, native 4C‐seq and CRISPR genome editing reveal functional hierarchies and chromatin looping dynamics of cytokine‐inducible “master” enhancers that govern gene regulation during the early proinflammatory response.
IL‐1α exposure remodels genome‐wide chromatin accessibility via TAK1 and NF‐κB.
Multiple dynamic and pre‐established 3D chromatin interactions facilitate the IL‐1α response.
Single‐enhancer deletion or activation reveal hierarchical control of the major human chemokine locus and inflammatory secretome.
Prelooped enhancers act across TADs to repress or activate TNFα‐regulated genes.
ATAC‐seq, native 4C‐seq and CRISPR genome editing reveal functional hierarchies and chromatin looping dynamics of cytokine‐inducible “master” enhancers that govern gene regulation during the early proinflammatory response.
Paracaspase MALT1 regulates glioma cell survival by controlling endo‐lysosome homeostasis