Abstract:
:Human telomerase reverse transcriptase (hTERT), a catalytic subunit of telomerase, is the primary determinant for telomerase enzyme activity, which has been associated with cellular immortality. Expression of the hTERT gene is regulated by various extracellular (external) stimuli and is aberrantly up-regulated in more than 90% of cancers. Here we show that hTERT gene expression was repressed in response to transforming growth factor-β (TGF-β) by a mechanism dependent on transcription factors Snail and c-Myc. TGF-β activated Snail and down-regulated c-Myc gene expression. In addition, ectopic expression of Snail strongly inhibited hTERT promoter activity, although co-expression of c-Myc abrogated this effect. Chromatin immunoprecipitation (ChIP) analysis revealed that TGF-β decreased c-Myc occupancy and dramatically increased recruitment of Snail to the E-box motifs of the hTERT promoter, thereby repressing hTERT expression. Our findings suggest a dynamic alteration in hTERT promoter occupancy by Snail and c-Myc is the mechanistic basis for TGF-β-mediated regulation of hTERT.
journal_name
Biochem Biophys Res Communjournal_title
Biochemical and biophysical research communicationsauthors
Yoo YS,Park S,Gwak J,Ju BG,Oh Sdoi
10.1016/j.bbrc.2015.07.146subject
Has Abstractpub_date
2015-09-11 00:00:00pages
131-6issue
1eissn
0006-291Xissn
1090-2104pii
S0006-291X(15)30376-4journal_volume
465pub_type
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journal_title:Biochemical and biophysical research communications
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journal_title:Biochemical and biophysical research communications
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