Template activating factor-I epigenetically regulates the TERT transcription in human cancer cells

Sci Rep. 2021 Sep 6;11(1):17726. doi: 10.1038/s41598-021-97009-9.

Abstract

Telomere, the terminus of linear chromosome in eukaryotes, is composed of specific repeat DNA which is mainly synthesized by a protein complex called telomerase. The maintenance of telomere DNA is important for unlimited proliferative capacity of cancer cells. The telomerase activity is controlled by the expression level of telomerase reverse transcriptase (TERT), a catalytic unit of telomerase, in some species including human. Therefore, to reveal the regulatory mechanisms of the transcription of TERT gene is important for understanding the tumor development. We found that template activating factor-I (TAF-I), a multifunctional nuclear protein, is involved in the transcriptional activation of TERT for the maintenance of telomere DNA in HeLa cells. TAF-I maintains the histone H3 modifications involved in transcriptional activation and hypomethylated cytosines in CpG dinucleotides around the transcription start site (TSS) in the TERT gene locus. Collectively, TAF-I is involved in the maintenance of telomere DNA through the regulation of TERT transcription, then consequently the occurrence and/or recurrence of cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Methylation
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Epigenesis, Genetic*
  • Gene Expression Regulation, Neoplastic
  • HeLa Cells
  • Histone Chaperones / genetics
  • Histone Chaperones / metabolism*
  • Histones / metabolism
  • Humans
  • Telomerase / genetics
  • Telomerase / metabolism*

Substances

  • DNA-Binding Proteins
  • Histone Chaperones
  • Histones
  • SET protein, human
  • TERT protein, human
  • Telomerase