Telomere length-dependent transcription and epigenetic modifications in promoters remote from telomere ends

Ananda Kishore Mukherjee, Shalu Sharma, Suman Sengupta, Dhurjhoti Saha, Pankaj Kumar, Tabish Hussain, Vivek Srivastava, Sumitabho Deb Roy, Jerry W. Shay, Shantanu Chowdhury

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Telomere-binding proteins constituting the shelterin complex have been studied primarily for telomeric functions. However, mounting evidence shows non-telomeric binding and gene regulation by shelterin factors. This raises a key question—do telomeres impact binding of shelterin proteins at distal non-telomeric sites? Here we show that binding of the telomere-repeat-binding-factor-2 (TRF2) at promoters ~60 Mb from telomeres depends on telomere length in human cells. Promoter TRF2 occupancy was depleted in cells with elongated telomeres resulting in altered TRF2-mediated transcription of distal genes. In addition, histone modifications—activation (H3K4me1 and H3K4me3) as well as silencing marks (H3K27me3)—at distal promoters were telomere length-dependent. These demonstrate that transcription, and the epigenetic state, of telomere-distal promoters can be influenced by telomere length. Molecular links between telomeres and the extra-telomeric genome, emerging from findings here, might have important implications in telomere-related physiology, particularly ageing and cancer.

Original languageEnglish (US)
Article numbere1007782
JournalPLoS genetics
Volume14
Issue number11
DOIs
StatePublished - Nov 2018

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

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    Mukherjee, A. K., Sharma, S., Sengupta, S., Saha, D., Kumar, P., Hussain, T., Srivastava, V., Roy, S. D., Shay, J. W., & Chowdhury, S. (2018). Telomere length-dependent transcription and epigenetic modifications in promoters remote from telomere ends. PLoS genetics, 14(11), [e1007782]. https://doi.org/10.1371/journal.pgen.1007782