Human telomerase reverse transcriptase (hTERT) transcription requires Sp1/Sp3 binding to the promoter and a permissive chromatin environment [DNA and Chromosomes]

October 20th, 2015 by Cheng, D., Zhao, Y., Wang, S., Jia, W., Kang, J., Zhu, J.

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 BAC reporters containing 160-kb of human genomic sequence containing the hTERT gene. Upon chromosomal integration, the BACs 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 -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: while GC-boxes were essential for promoter activity, factors bound to the E-boxes functioned to de-repress hTERT promoter.
  • Posted in Journal of Biological Chemistry, Publications
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