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

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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 1 2018

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ASJC Scopus subject areas

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

Cite this

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