BMAL1 associates with chromosome ends to control rhythms in TERRA and telomeric heterochromatin

• Published in: PloS one 2019-10, Vol.14 (10), p.e0223803-e0223803
• Main Authors: Park, Jinhee, Zhu, Qiaoqiao, Mirek, Emily, Na, Li, Raduwan, Hamidah, Anthony, Tracy G, Belden, William J
• Format: Article
• Language: English
• Subjects: Age; Aging; Animal sciences; Animals; ARNTL Transcription Factors - physiology; Attrition; Biological clocks; Biology and Life Sciences; BMAL1 protein; Cellular Senescence; Chromosomes; Chromosomes - physiology; Chronic diseases; Chronic illnesses; Circadian Rhythm; Circadian rhythms; Danio rerio; Deoxyribonucleic acid; Disruption; Diurnal; DNA; DNA binding proteins; DNA methylation; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; EDTA; Feedback; Female; Fibroblasts; Gene expression; Gene Expression Regulation; Genetic aspects; Health aspects; Heterochromatin; Heterochromatin - physiology; Homeostasis; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Neurospora; Physiology; Properties; Proteins; Repetitive Sequences, Nucleic Acid; Research and Analysis Methods; Ribonucleic acid; RNA; Senescence; Telomerase; Telomere - genetics; Telomeres; Transcription (Genetics); Transcription factors; Transcription Factors - genetics; Transcription Factors - metabolism; Zebrafish
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0223803

The circadian clock and aging are intertwined. Disruption to the normal diurnal rhythm accelerates aging and corresponds with telomere shortening. Telomere attrition also correlates with increase cellular senescence and incidence of chronic disease. In this report, we examined diurnal association of White Collar 2 (WC-2) in Neurospora and BMAL1 in zebrafish and mice and found that these circadian transcription factors associate with telomere DNA in a rhythmic fashion. We also identified a circadian rhythm in Telomeric Repeat-containing RNA (TERRA), a lncRNA transcribed from the telomere. The diurnal rhythm in TERRA was lost in the liver of Bmal1-/- mice indicating it is a circadian regulated transcript. There was also a BMAL1-dependent rhythm in H3K9me3 at the telomere in zebrafish brain and mouse liver, and this rhythm was lost with increasing age. Taken together, these results provide evidence that BMAL1 plays a direct role in telomere homeostasis by regulating rhythms in TERRA and heterochromatin. Loss of these rhythms may contribute to telomere erosion during aging.