Krüppel-like factor 2 represses transcription of the telomerase catalytic subunit human telomerase reverse transcriptase (hTERT) in human T cells

J Biol Chem. 2015 Apr 3;290(14):8758-63. doi: 10.1074/jbc.M114.610386. Epub 2015 Feb 18.

Abstract

In normal human T cells, telomerase activity is strictly regulated. T cells are thought to express telomerase to avoid replicative senescence, unlike most normal somatic cells with definite replicative lifespan. T cells in blood and tissues are usually in a state of quiescence without expression of the limiting catalytic subunit of telomerase, human telomerase reverse transcriptase (hTERT). In contrast to activation, repression of hTERT transcription has not been studied well. Our previous studies have found an hTERT promoter element with repressive function. Here we identified KLF2, which represses hTERT transcription by binding to the putative promoter element. KLF2 and hTERT exhibited reciprocal mRNA expression patterns in primary human T cells. In activated T cells, KLF2 binding to the hTERT promoter was eliminated, relieving the repression of hTERT transcription found in resting T cells. Our results suggest that KLF2 is involved in strict repression of hTERT expression through binding to the promoter in primary human T cells.

Keywords: Krüppel-like Factor 2 (KLF2); T-cells; Telomerase Reverse Transcriptase (TERT); Transcription; Transcription Repressor; Zinc Finger.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Blotting, Western
  • Catalytic Domain
  • Cells, Cultured
  • DNA Primers
  • Electrophoretic Mobility Shift Assay
  • Humans
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / physiology*
  • Polymerase Chain Reaction
  • RNA, Small Interfering / genetics
  • T-Lymphocytes / enzymology*
  • Telomerase / chemistry
  • Telomerase / genetics
  • Telomerase / metabolism*
  • Transcription, Genetic / physiology*

Substances

  • DNA Primers
  • KLF2 protein, human
  • Kruppel-Like Transcription Factors
  • RNA, Small Interfering
  • TERT protein, human
  • Telomerase