TNFα signals through specialized factories where responsive coding and miRNA genes are transcribed

被引：99

作者：

Papantonis, Argyris ^{[2
]}

Kohro, Takahide ^{[3
]}

Baboo, Sabyasachi ^{[2
]}

Larkin, Joshua D. ^{[2
]}

Deng, Binwei ^{[2
]}

Short, Patrick ^{[2
,4
]}

Tsutsumi, Shuichi ^{[1
]}

Taylor, Stephen ^{[5
]}

Kanki, Yasuharu ^{[1
]}

Kobayashi, Mika ^{[1
]}

Li, Guoliang ^{[6
]}

Poh, Huay-Mei ^{[6
]}

Ruan, Xiaoan ^{[6
]}

Aburatani, Hiroyuki ^{[1
]}

Ruan, Yijun ^{[6
]}

Kodama, Tatsuhiko ^{[1
]}

Wada, Youichiro ^{[1
]}

Cook, Peter R. ^{[2
]}

机构：

[1] Univ Tokyo, Adv Sci & Technol Res Ctr, Lab Syst Biol & Med, Meguru Ku, Tokyo 1538904, Japan

[2] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England

[3] Univ Tokyo, Grad Sch Med, Dept Translat Res Healthcare & Clin Sci, Tokyo 1538904, Japan

[4] Univ N Carolina, Dept Appl Math & Quantitat Biol, Chapel Hill, NC USA

[5] Univ Oxford, Computat Res Biol Grp, Oxford, England

[6] Genome Inst Singapore, Singapore, Singapore

来源：

EMBO JOURNAL | 2012年 / 31卷 / 23期

基金：

英国医学研究理事会; 英国生物技术与生命科学研究理事会; 英国惠康基金;

关键词：

chromosome conformation capture; cytokine signalling; nuclear factor kappa B (NF kappa B); RNA polymerase; tumour necrosis factor alpha (TNF alpha); transcription factory; CHROMOSOME CONFORMATION CAPTURE; CHROMATIN; EXPRESSION; SITES; RNA; CELL; ENHANCERS; MICRORNAS; INSIGHTS; MODEL;

D O I：

10.1038/emboj.2012.288

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Tumour necrosis factor alpha (TNF alpha) is a potent cytokine that signals through nuclear factor kappa B (NF kappa B) to activate a subset of human genes. It is usually assumed that this involves RNA polymerases transcribing responsive genes wherever they might be in the nucleus. Using primary human endothelial cells, variants of chromosome conformation capture (including 4C and chromatin interaction analysis with paired-end tag sequencing), and fluorescence in situ hybridization to detect single nascent transcripts, we show that TNF alpha induces responsive genes to congregate in discrete 'N F kappa B factories'. Some factories further specialize in transcribing responsive genes encoding micro-RNAs that target downregulated mRNAs. We expect all signalling pathways to contain this extra leg, where responding genes are transcribed in analogous specialized factories. The EMBO Journal (2012) 31, 4404-4414. doi:10.1038/emboj.2012.288; Published online 26 October 2012

引用

页码：4404 / 4414

页数：11

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