Chromatin dynamics at the hTERT promoter during transcriptional activation and repression by c-Myc and Mnt in Xenopus leavis oocytes

Exp Cell Res. 2013 Dec 10;319(20):3160-9. doi: 10.1016/j.yexcr.2013.07.004. Epub 2013 Jul 13.


The transcription factors c-Myc and Mnt regulate gene expression through dimerization with Max and binding to E-boxes in target genes. While c-Myc activates gene expression via recruitment of histone modifying complexes, Mnt acts as a transcriptional repressor. Here, we used the Xenopus leavis oocyte system to address the effect of c-Myc and Mnt on transcription and chromatin remodeling over the E-box region in the human telomerase reverse transcriptase (hTERT) promoter. As expected we found elevated and decreased levels of hTERT transcription upon exogenously expressed c-Myc/Max and Mnt/Max, respectively. In addition, we confirmed binding of these heterodimers to both E-boxes already enriched with H3K9ac and H4K16ac. These chromatin marks were further enhanced upon c-Myc/Max binding followed by increased DNA accessibility in the E-box region. In contrast, Mnt/Max inhibited Myc-induced transcription and mediated repression through complete chromatin condensation and deacetylation of H3K9 and H4K16 across the E-box region. Importantly, Mnt was able to counteract c-Myc mediated activation even when expressed at low levels, suggesting Mnt to act as a strong repressor by closing the chromatin structure. Collectively our data demonstrate that the balance between c-Myc and Mnt activity determines the transcriptional outcome of the hTERT promoter by modulation of the chromatin architecture.

Keywords: AU; Ac; ChIP; Chromatin remodeling; DMS; DNase I; EMSA; HAT; HDAC; HEK293T; Histone modification; Mnt; Transcription; WB; Western Blot; acetylation; arbitrary units; bHLHZip; basepair; basic helix loop helix leucine zipper; bp; c-Myc; chromatin immunoprecipitation; deoxyribonuclease I; dimethylsulfate; double stranded DNA; dsDNA; electrophoretic mobility shift assay; hTERT; hTERT promoter; histone acetylase; histone deacetylase; human embryonic kidney 293T; human telomerase reverse transcriptase; single stranded DNA; ssDNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism*
  • Cells, Cultured
  • Chromatin / genetics
  • Chromatin / metabolism*
  • HEK293 Cells
  • Humans
  • Oocytes / cytology
  • Oocytes / metabolism*
  • Promoter Regions, Genetic / genetics*
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Telomerase / genetics*
  • Transcription, Genetic / genetics*
  • Xenopus laevis


  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Chromatin
  • MNT protein, human
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger
  • Repressor Proteins
  • TERT protein, human
  • Telomerase