NF-κB modifies the mammalian circadian clock through interaction with the core clock protein BMAL1 Article Swipe
Yang Shen
,
Mehari Endale
,
Wei Wang
,
Andrew R. Morris
,
Lauren J. Francey
,
Rachel L. Harold
,
David W. Hammers
,
Zhiguang Huo
,
Carrie L. Partch
,
John B. Hogenesch
,
Zhao‐Hui Wu
,
Andrew C. Liu
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1371/journal.pgen.1009933
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1371/journal.pgen.1009933
In mammals, the circadian clock coordinates cell physiological processes including inflammation. Recent studies suggested a crosstalk between these two pathways. However, the mechanism of how inflammation affects the clock is not well understood. Here, we investigated the role of the proinflammatory transcription factor NF-κB in regulating clock function. Using a combination of genetic and pharmacological approaches, we show that perturbation of the canonical NF-κB subunit RELA in the human U2OS cellular model altered core clock gene expression. While RELA activation shortened period length and dampened amplitude, its inhibition lengthened period length and caused amplitude phenotypes. NF-κB perturbation also altered circadian rhythms in the master suprachiasmatic nucleus (SCN) clock and locomotor activity behavior under different light/dark conditions. We show that RELA, like the clock repressor CRY1, repressed the transcriptional activity of BMAL1/CLOCK at the circadian E-box cis-element. Biochemical and biophysical analysis showed that RELA binds to the transactivation domain of BMAL1. These data support a model in which NF-kB competes with CRY1 and coactivator CBP/p300 for BMAL1 binding to affect circadian transcription. This is further supported by chromatin immunoprecipitation analysis showing that binding of RELA, BMAL1 and CLOCK converges on the E-boxes of clock genes. Taken together, these data support a significant role for NF-κB in directly regulating the circadian clock and highlight mutual regulation between the circadian and inflammatory pathways.
Related Topics
Concepts
Circadian clock
Biology
Circadian rhythm
Suprachiasmatic nucleus
Cryptochrome
CLOCK
Cell biology
Transactivation
Chromatin immunoprecipitation
Transcription factor
PER1
Genetics
Gene expression
Neuroscience
Gene
Promoter
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1371/journal.pgen.1009933
- https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1009933&type=printable
- OA Status
- gold
- Cited By
- 72
- References
- 101
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3217180261
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W3217180261Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1371/journal.pgen.1009933Digital Object Identifier
- Title
-
NF-κB modifies the mammalian circadian clock through interaction with the core clock protein BMAL1Work title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2021Year of publication
- Publication date
-
2021-11-22Full publication date if available
- Authors
-
Yang Shen, Mehari Endale, Wei Wang, Andrew R. Morris, Lauren J. Francey, Rachel L. Harold, David W. Hammers, Zhiguang Huo, Carrie L. Partch, John B. Hogenesch, Zhao‐Hui Wu, Andrew C. LiuList of authors in order
- Landing page
-
https://doi.org/10.1371/journal.pgen.1009933Publisher landing page
- PDF URL
-
https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1009933&type=printableDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1009933&type=printableDirect OA link when available
- Concepts
-
Circadian clock, Biology, Circadian rhythm, Suprachiasmatic nucleus, Cryptochrome, CLOCK, Cell biology, Transactivation, Chromatin immunoprecipitation, Transcription factor, PER1, Genetics, Gene expression, Neuroscience, Gene, PromoterTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
72Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 25, 2024: 14, 2023: 19, 2022: 14Per-year citation counts (last 5 years)
- References (count)
-
101Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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