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


Autoři: Jinhee Park aff001;  Qiaoqiao Zhu aff001;  Emily Mirek aff002;  Li Na aff001;  Hamidah Raduwan aff001;  Tracy G. Anthony aff002;  William J. Belden aff001
Působiště autorů: Department of Animal Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, United States of America aff001;  Department of Nutritional Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, United States of America aff002
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: 10.1371/journal.pone.0223803

Souhrn

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.

Klíčová slova:

Circadian oscillators – Circadian rhythms – Mammalian genomics – Telomeres – Zebrafish – Heterochromatin – Neurospora – Northern blot


Zdroje

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