RNA Polymerase II Regulates Topoisomerase 1 Activity to Favor Efficient Transcription

被引：186

作者：

Baranello, Laura ^{[1
]}

Wojtowicz, Damian ^{[2
]}

Cui, Kairong ^{[3
]}

Devaiah, Ballachanda N. ^{[4
]}

Chung, Hye-Jung ^{[1
]}

Chan-Salis, Ka Yim ^{[5
]}

Guha, Rajarshi ^{[6
]}

Wilson, Kelli ^{[6
]}

Zhang, Xiaohu ^{[6
]}

Zhang, Hongliang ^{[7
,8
]}

Piotrowski, Jason ^{[9
]}

Thomas, Craig J. ^{[6
]}

Singer, Dinah S. ^{[4
]}

Pugh, B. Franklin ^{[5
]}

Pommier, Yves ^{[7
,8
]}

Przytycka, Teresa M. ^{[2
]}

Kouzine, Fedor ^{[1
]}

Lewis, Brian A. ^{[9
]}

Zhao, Keji ^{[3
]}

Levens, David ^{[1
]}

机构：

[1] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA

[2] NCBI, Computat Biol Branch, NIH, Bethesda, MD 20892 USA

[3] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA

[4] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA

[5] Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA

[6] NCATS, Div Preclin Innovat, NIH, Rockville, MD 20850 USA

[7] NCI, Dev Therapeut Branch, NIH, Bethesda, MD 20892 USA

[8] NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA

[9] NCI, Lymphoid Malignancies Branch, NIH, Bethesda, MD 20892 USA

来源：

CELL | 2016年 / 165卷 / 02期

关键词：

BROMODOMAIN PROTEIN BRD4; CARBOXY-TERMINAL DOMAIN; P-TEFB; IN-VIVO; DEPENDENT TRANSCRIPTION; SELECTIVE-INHIBITION; CLEAVAGE COMPLEXES; PAUSE RELEASE; GENOME-WIDE; CTD CODE;

D O I：

10.1016/j.cell.2016.02.036

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：

We report a mechanism through which the transcription machinery directly controls topoisomerase 1 (TOP1) activity to adjust DNA topology throughout the transcription cycle. By comparing TOP1 occupancy using chromatin immunoprecipitation sequencing (ChIP-seq) versus TOP1 activity using topoisomerase 1 sequencing (TOP1-seq), a method reported here to map catalytically engaged TOP1, TOP1 bound at promoters was discovered to become fully active only after pause-release. This transition coupled the phosphorylation of the carboxyl-terminal-domain (CTD) of RNA polymerase II (RNAPII) with stimulation of TOP1 above its basal rate, enhancing its processivity. TOP1 stimulation is strongly dependent on the kinase activity of BRD4, a protein that phosphorylates Ser2-CTD and regulates RNAPII pause-release. Thus the coordinated action of BRD4 and TOP1 overcame the torsional stress opposing transcription as RNAPII commenced elongation but preserved negative supercoiling that assists promotermelting at start sites. This nexus between transcription and DNA topology promises to elicit new strategies to intercept pathological gene expression.

引用

页码：357 / 371

页数：15

共 74 条

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