[DEBUG-WINDOW 처리영역 보기]
즐겨찾기  |  뉴스레터  |  오늘의 정보  |  e브릭몰e브릭몰 회원가입   로그인
BRIC홈 한국을 빛내는 사람들
실험복 제공
스폰서배너광고 안내  배너1 배너2 배너3
전체보기 추천논문 상위피인용논문 인터뷰 그이후 한빛사통계
박성호
박성호 (Sung Ho Park) 저자 이메일 보기
Hospital for Special Surgery
 
조회 468  인쇄하기 주소복사 트위터 공유 페이스북 공유 
TNF-induced inflammatory genes escape repression in fibroblast-like synoviocytes: transcriptomic and epigenomic analysis
열기 Authors and Affiliations

Abstract

Objective : We investigated genome-wide changes in gene expression and chromatin remodelling induced by tumour necrosis factor (TNF) in fibroblast-like synoviocytes (FLS) and macrophages to better understand the contribution of FLS to the pathogenesis of rheumatoid arthritis (RA).

Methods : FLS were purified from patients with RA and CD14+ human monocyte-derived macrophages were obtained from healthy donors. RNA-sequencing, histone 3 lysine 27 acetylation (H3K27ac), chromatin immunoprecipitation-sequencing (ChIP-seq) and assay for transposable accessible chromatin by high throughput sequencing (ATAC-seq) were performed in control and TNF-stimulated cells.

Results : We discovered 280 TNF-inducible arthritogenic genes which are transiently expressed and subsequently repressed in macrophages, but in RA, FLS are expressed with prolonged kinetics that parallel the unremitting kinetics of RA synovitis. 80 out of these 280 fibroblast-sustained genes (FSGs) that escape repression in FLS relative to macrophages were desensitised (tolerised) in macrophages. Epigenomic analysis revealed persistent H3K27 acetylation and increased chromatin accessibility in regulatory elements associated with FSGs in TNF-stimulated FLS. The accessible regulatory elements of FSGs were enriched in binding motifs for nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), interferon-regulatory factors (IRFs) and activating protein-1 (AP-1). Inhibition of bromodomain and extra-terminal motif (BET) proteins, which interact with histone acetylation, suppressed sustained induction of FSGs by TNF.

Conclusion : Our genome-wide analysis has identified the escape of genes from transcriptional repression in FLS as a novel mechanism potentially contributing to the chronic unremitting synovitis observed in RA. Our finding that TNF induces sustained chromatin activation in regulatory elements of the genes that escape repression in RA FLS suggests that altering or targeting chromatin states in FLS (eg, with inhibitors of BET proteins) is an attractive therapeutic strategy.

논문정보
- 형식: Research article
- 게재일: 2019년 08월 (BRIC 등록일 2019-08-02)
- 연구진: 국외연구진
- 분야: Medicine
RNA 기반의 합성생물학 유전자회로(synthetic gene circuits) 디자인[Nat. Chem. Biol.]
김종민
발표: 김종민 (POSTECH)
일자: 2020년 1월 6일 (월) 오후 02시 (한국시간)
언어: 영어
참석자 접수신청하기
수학울렁증에 대한 인지신경과학적 접근[Sci. Adv.]
최경환
발표: 최경환 (University of Chicago)
일자: 2019년 12월 19일 (목) 오후 02시 (한국시간)
언어: 한국어
참석자 접수신청하기

  댓글 0
등록
 
목록
(주)루미나노
관련링크
박성호 님 전체논문보기 >
관련인물
박민경현 (Hospital for S...)
관련분야 논문보기
Medicine

외부링크
Google (by Sung Ho Park)
Pubmed (by Sung Ho Park)
프리미엄 Bio일정 Bio일정 프리미엄 안내
2019 미래인재 심포지엄
2019 미래인재 심포지엄
날짜: 2019.12.16
장소: 더케이호텔 서울3층 거문고홀 등
(다부처 공동기획)원스톱 CAR치료제 개발 지원 플랫폼 구축을 위한 공청회
[BRIC Webinar]수학울렁증에 대한 인지신경과학적 접근[Sci. Adv.]
[BRIC Webinar]수학울렁증에 대한 인지신경과학적 접근[Sci. Adv.]
사전접수: ~2019.12.18
날짜: 2019.12.19
Online 개최
[무료/취업연계]바이오QC 실무과정 8기 모집
[무료/취업연계]바이오QC 실무과정 8기 모집
사전접수: ~2020.01.06
날짜: 2020.03.02~06.12
장소: 성남시 분당구 황새울로
위로가기
한빛사 홈  |  한빛사FAQ  |  한빛사 문의 및 제안
 |  BRIC소개  |  이용안내  |  이용약관  |  개인정보처리방침  |  이메일무단수집거부
Copyright © BRIC. All rights reserved.  |  문의 member@ibric.org
트위터 트위터    페이스북 페이스북   유튜브 유튜브    RSS서비스 RSS
머크