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Telomere length-dependent transcription and epigenetic modifications in promoters remote from telomere ends.
oleh: Ananda Kishore Mukherjee, Shalu Sharma, Shalu Sharma, Suman Sengupta, Dhurjhoti Saha, Pankaj Kumar, Tabish Hussain, Vivek Srivastava, Sumitabho Deb Roy, Jerry W Shay, Shantanu Chowdhury, Shantanu Chowdhury
Format: | Article |
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Diterbitkan: | Public Library of Science (PLoS) 2018-11-01 |
Deskripsi
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.