Cargando…

BMAL1 modulates senescence programming via AP-1

Cellular senescence and circadian dysregulation are biological hallmarks of aging. Whether they are coordinately regulated has not been thoroughly studied. We hypothesize that BMAL1, a pioneer transcription factor and master regulator of the molecular circadian clock, plays a role in the senescence...

Descripción completa

Detalles Bibliográficos
Autores principales: Jachim, Sarah K., Zhong, Jian, Ordog, Tamas, Lee, Jeong-Heon, Bhagwate, Aditya V., Nagaraj, Nagaswaroop Kengunte, Westendorf, Jennifer J., Passos, João F., Matveyenko, Aleksey V., LeBrasseur, Nathan K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10599731/
https://www.ncbi.nlm.nih.gov/pubmed/37819791
http://dx.doi.org/10.18632/aging.205112
_version_ 1785125828870275072
author Jachim, Sarah K.
Zhong, Jian
Ordog, Tamas
Lee, Jeong-Heon
Bhagwate, Aditya V.
Nagaraj, Nagaswaroop Kengunte
Westendorf, Jennifer J.
Passos, João F.
Matveyenko, Aleksey V.
LeBrasseur, Nathan K.
author_facet Jachim, Sarah K.
Zhong, Jian
Ordog, Tamas
Lee, Jeong-Heon
Bhagwate, Aditya V.
Nagaraj, Nagaswaroop Kengunte
Westendorf, Jennifer J.
Passos, João F.
Matveyenko, Aleksey V.
LeBrasseur, Nathan K.
author_sort Jachim, Sarah K.
collection PubMed
description Cellular senescence and circadian dysregulation are biological hallmarks of aging. Whether they are coordinately regulated has not been thoroughly studied. We hypothesize that BMAL1, a pioneer transcription factor and master regulator of the molecular circadian clock, plays a role in the senescence program. Here, we demonstrate BMAL1 is significantly upregulated in senescent cells and has altered rhythmicity compared to non-senescent cells. Through BMAL1-ChIP-seq, we show that BMAL1 is uniquely localized to genomic motifs associated with AP-1 in senescent cells. Integration of BMAL1-ChIP-seq data with RNA-seq data revealed that BMAL1 presence at AP-1 motifs is associated with active transcription. Finally, we showed that BMAL1 contributes to AP-1 transcriptional control of key features of the senescence program, including altered regulation of cell survival pathways, and confers resistance to drug-induced apoptosis. Overall, these results highlight a previously unappreciated role of the core circadian clock component BMAL1 on the molecular phenotype of senescent cells.
format Online
Article
Text
id pubmed-10599731
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Impact Journals
record_format MEDLINE/PubMed
spelling pubmed-105997312023-10-26 BMAL1 modulates senescence programming via AP-1 Jachim, Sarah K. Zhong, Jian Ordog, Tamas Lee, Jeong-Heon Bhagwate, Aditya V. Nagaraj, Nagaswaroop Kengunte Westendorf, Jennifer J. Passos, João F. Matveyenko, Aleksey V. LeBrasseur, Nathan K. Aging (Albany NY) Research Paper Cellular senescence and circadian dysregulation are biological hallmarks of aging. Whether they are coordinately regulated has not been thoroughly studied. We hypothesize that BMAL1, a pioneer transcription factor and master regulator of the molecular circadian clock, plays a role in the senescence program. Here, we demonstrate BMAL1 is significantly upregulated in senescent cells and has altered rhythmicity compared to non-senescent cells. Through BMAL1-ChIP-seq, we show that BMAL1 is uniquely localized to genomic motifs associated with AP-1 in senescent cells. Integration of BMAL1-ChIP-seq data with RNA-seq data revealed that BMAL1 presence at AP-1 motifs is associated with active transcription. Finally, we showed that BMAL1 contributes to AP-1 transcriptional control of key features of the senescence program, including altered regulation of cell survival pathways, and confers resistance to drug-induced apoptosis. Overall, these results highlight a previously unappreciated role of the core circadian clock component BMAL1 on the molecular phenotype of senescent cells. Impact Journals 2023-10-10 /pmc/articles/PMC10599731/ /pubmed/37819791 http://dx.doi.org/10.18632/aging.205112 Text en Copyright: © 2023 Jachim et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Jachim, Sarah K.
Zhong, Jian
Ordog, Tamas
Lee, Jeong-Heon
Bhagwate, Aditya V.
Nagaraj, Nagaswaroop Kengunte
Westendorf, Jennifer J.
Passos, João F.
Matveyenko, Aleksey V.
LeBrasseur, Nathan K.
BMAL1 modulates senescence programming via AP-1
title BMAL1 modulates senescence programming via AP-1
title_full BMAL1 modulates senescence programming via AP-1
title_fullStr BMAL1 modulates senescence programming via AP-1
title_full_unstemmed BMAL1 modulates senescence programming via AP-1
title_short BMAL1 modulates senescence programming via AP-1
title_sort bmal1 modulates senescence programming via ap-1
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10599731/
https://www.ncbi.nlm.nih.gov/pubmed/37819791
http://dx.doi.org/10.18632/aging.205112
work_keys_str_mv AT jachimsarahk bmal1modulatessenescenceprogrammingviaap1
AT zhongjian bmal1modulatessenescenceprogrammingviaap1
AT ordogtamas bmal1modulatessenescenceprogrammingviaap1
AT leejeongheon bmal1modulatessenescenceprogrammingviaap1
AT bhagwateadityav bmal1modulatessenescenceprogrammingviaap1
AT nagarajnagaswaroopkengunte bmal1modulatessenescenceprogrammingviaap1
AT westendorfjenniferj bmal1modulatessenescenceprogrammingviaap1
AT passosjoaof bmal1modulatessenescenceprogrammingviaap1
AT matveyenkoalekseyv bmal1modulatessenescenceprogrammingviaap1
AT lebrasseurnathank bmal1modulatessenescenceprogrammingviaap1