NDLI: Human Telomerase Reverse Transcriptase (hTERT) Transcription Requires Sp1/Sp3 Binding to the Promoter and a Permissive Chromatin Environment.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Zhao, Yuanjun Jia, Wenwen Cheng, De Wang, Shuwen Kang, Jiuhong Zhu, Jiyue
Description	Author Affiliation: Cheng D ( From the Department of Pharmaceutical Sciences, Washington State University College of Pharmacy, Spokane, Washington 99210.); Zhao Y ( the Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, and.); Wang S ( From the Department of Pharmaceutical Sciences, Washington State University College of Pharmacy, Spokane, Washington 99210.); Jia W ( the School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.); Kang J ( the School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.); Zhu J ( From the Department of Pharmaceutical Sciences, Washington State University College of Pharmacy, Spokane, Washington 99210, the Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, and jiyue.zhu@wsu.edu.)
Abstract	The transcription of human telomerase gene hTERT is regulated by transcription factors (TFs), including Sp1 family proteins, and its chromatin environment. To understand its regulation in a relevant chromatin context, we employed bacterial artificial chromosome reporters containing 160 kb of human genomic sequence containing the hTERT gene. Upon chromosomal integration, the bacterial artificial chromosomes recapitulated endogenous hTERT expression, contrary to transient reporters. Sp1/Sp3 expression did not correlate with hTERT promoter activity, and these TFs bound to the hTERT promoters in both telomerase-positive and telomerase-negative cells. Mutation of the proximal GC-box resulted in a dramatic decrease of hTERT promoter activity, and mutations of all five GC-boxes eliminated its transcriptional activity. Neither mutations of GC-boxes nor knockdown of endogenous Sp1 impacted promoter binding by other TFs, including E-box-binding proteins, and histone acetylation and trimethylation of histone H3K9 at the hTERT promoter in telomerase-positive and -negative cells. The result indicated that promoter binding by Sp1/Sp3 was essential, but not a limiting step, for hTERT transcription. hTERT transcription required a permissive chromatin environment. Importantly, our data also revealed different functions of GC-boxes and E-boxes in hTERT regulation; although GC-boxes were essential for promoter activity, factors bound to the E-boxes functioned to de-repress hTERT promoter.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	50
Volume Number	290
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2015-12-11
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Chromatin Metabolism Promoter Regions, Genetic Sp1 Transcription Factor Sp3 Transcription Factor Telomerase Genetics Transcription, Genetic Cell Line Protein Binding Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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