学科主题临床医学
Dismissal of RNA Polymerase II Underlies a Large Ligand-Induced Enhancer Decommissioning Program
Tan, Yuliang1; Jin, Chunyu1; Ma, Wubin1; Hu, Yiren1; Tanasa, Bogdan2; Oh, Soohwan1,3; Gamliel, Amir1; Ma, Qi1,4; Yao, Lu1,5; Zhang, Jie1; Ohgi, Kenny1; Liu, Wen1,6; Aggarwal, Aneel K.7; Rosenfeld, Michael G.1
通讯作者Rosenfeld, Michael G.(1)
刊名MOLECULAR CELL
2018-08-16
DOI10.1016/j.molcel.2018.07.039
71期:4页:526-+
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology ; Cell Biology
研究领域[WOS]Biochemistry & Molecular Biology ; Cell Biology
关键词[WOS]PLURIPOTENT STEM-CELLS ; DNA-BINDING DOMAIN ; ESTROGEN-RECEPTOR ; GENE-EXPRESSION ; BREAST-CANCER ; HUMAN GENOME ; TRANSCRIPTIONAL ACTIVATION ; CHROMATIN INTERACTIONS ; READ ALIGNMENT ; HISTONE H3
英文摘要

Nuclear receptors induce both transcriptional activation and repression programs responsible for development, homeostasis, and disease. Here, we report a previously overlooked enhancer decommissioning strategy underlying a large estrogen receptor alpha (ER alpha)-dependent transcriptional repression program. The unexpected signature for this E-2-induced program resides in indirect recruitment of ER alpha to a large cohort of pioneer factor basally active FOXA1-bound enhancers that lack cognate ER alpha DNA-binding elements. Surprisingly, these basally active estrogen-repressed (BAER) enhancers are decommissioned by ER alpha-dependent recruitment of the histone demethylase KDM2A, functioning independently of its demethylase activity. Rather, KDM2A tethers the E3 ubiquitin-protein ligase NEDD4 to ubiquitylate/dismiss Pol II to abrogate eRNA transcription, with consequent target gene downregulation. Thus, our data reveal that Pol II ubiquitylation/dismissal may serve as a potentially broad strategy utilized by indirectly bound nuclear receptors to abrogate large programs of pioneer factor-mediated, eRNA-producing enhancers.

语种英语
WOS记录号WOS:000441745600007
通讯作者邮箱mrosenfeld@ucsd.edu
第一作者单位Univ Calif San Diego, Howard Hughes Med Inst, Dept Med, 9500 Gilman Dr, La Jolla, CA 92093 USA
通讯作者单位Univ Calif San Diego, Howard Hughes Med Inst, Dept Med, 9500 Gilman Dr, La Jolla, CA 92093 USA
ISSN1097-2765
引用统计
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/142891
专题北京大学临床肿瘤学院_乳腺癌预防治疗中心
作者单位1.Univ Calif San Diego, Howard Hughes Med Inst, Dept Med, 9500 Gilman Dr, La Jolla, CA 92093 USA;
2.Univ Calif San Diego, Biol Sci Grad Program, La Jolla, CA 92093 USA;
3.Univ Calif San Diego, Bioinformat & Syst Biol Grad Program, La Jolla, CA 92093 USA;
4.Peking Univ, Canc Hosp & Inst, Breast Ctr, Minist Educ,Key Lab Carcinogenesis & Translat Res, Beijing 100142, Peoples R China;
5.Xiamen Univ, Fujian Prov Key Lab Innovat Drug Target Res, Sch Pharmaceut Sci, Xiangan South Rd, Xiamen 361102, Fujian, Peoples R China;
6.Mt Sinai Sch Med, Dept Struct & Chem Biol, Box 1677,1425 Madison Ave, New York, NY 10029 USA;
7.Stanford Univ, Sch Med, 265 Campus Dr,LLSCR Bldg, Stanford, CA 94305 USA
推荐引用方式
GB/T 7714
Tan, Yuliang,Jin, Chunyu,Ma, Wubin,et al. Dismissal of RNA Polymerase II Underlies a Large Ligand-Induced Enhancer Decommissioning Program[J]. MOLECULAR CELL,2018,71(4):526-+.
APA Tan, Yuliang.,Jin, Chunyu.,Ma, Wubin.,Hu, Yiren.,Tanasa, Bogdan.,...&Rosenfeld, Michael G..(2018).Dismissal of RNA Polymerase II Underlies a Large Ligand-Induced Enhancer Decommissioning Program.MOLECULAR CELL,71(4),526-+.
MLA Tan, Yuliang,et al."Dismissal of RNA Polymerase II Underlies a Large Ligand-Induced Enhancer Decommissioning Program".MOLECULAR CELL 71.4(2018):526-+.
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