Volume 28, No 6, Jun 2018

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 28 Issue 6, June 2018: 670-685

ORIGINAL ARTICLES

SUMO suppresses and MYC amplifies transcription globally by regulating CDK9 sumoylation

Fang Yu ¹, Guang Shi ^1,5, Shimeng Cheng ¹, Jiwei Chen ¹, Shwu-Yuan Wu ²
, Zhiqiang Wang¹, Nansong Xia³, Yunhao Zhai¹,Zhenxing Wang¹, Yu Peng¹
, Dong Wang¹, James X. Du¹, Lujian Liao¹, Sheng-Zhong Duan⁴, Tieliu Shi¹, Jinke Cheng³,Cheng-Ming Chiang², Jiwen Li¹ and Jiemin Wong¹

¹Shanghai Key Laboratory of Regulatory Biology, Fengxian District Central Hospital-ECNU Joint Center of Translational Medicine, Institute of Biomedical Sciences and School of
Life Sciences, East China Normal University, Shanghai 200241, China; ² Simmons Comprehensive Cancer Center, Department of Biochemistry, and Department of Pharmacology,University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA; ³Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China and ⁴Laboratory of Oral Microbiology,Shanghai Research Institute of Stomatology, Shanghai Key Laboratory of Stomatology, Ninth People’s Hospital, School of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China⁵Present address: Key Laboratory of Gene Engineering of the Ministry of Education and Institute of Healthy Aging Research, School of Life Sciences, Sun Yat-sen University,Guangzhou 510275, China
Correspondence: Jiwen Li (jwli@bio.ecnu.edu.cn) or Jiemin Wong (jmweng@bio.ecnu.edu.cn)These authors contributed equally: Fang Yu, Guang Shi.

Regulation of transcription is fundamental to the control of cellular gene expression and function. Although recent studies have revealed a role for the oncoprotein MYC in amplifying global transcription, little is known as to how the global transcription is suppressed. Here we report that SUMO and MYC mediate opposite effects upon global transcription by controlling the level of CDK9 sumoylation. On one hand, SUMO suppresses global transcription via sumoylation of CDK9, the catalytic subunit of P-TEFb kinase essential for productive transcriptional elongation. On the other hand, MYC amplifies global transcription by antagonizing CDK9 sumoylation. Sumoylation of CDK9 blocks its interaction with Cyclin T1 and thus the formation of active P-TEFb complex. Transcription profiling analyses reveal that SUMO represses global transcription, particularly of moderately to highly expressed genes and by generating a sumoylation-resistant CDK9 mutant, we confirm that sumoylation of CDK9 inhibits global transcription. Together, our data reveal that SUMO and MYC oppositely control global gene expression by regulating the dynamic sumoylation and desumoylation of CDK9.

10.1038/s41422-018-0023-9

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