An NF-κB–driven lncRNA orchestrates colitis and circadian clock

We uncover a cycling and NF-κB–driven lncRNA (named Lnc-UC) that epigenetically modifies transcription of circadian clock gene Rev-erbα, thereby linking circadian clock to colitis. Cycling expression of Lnc-UC is generated by the central clock protein Bmal1 via an E-box element. NF-κB activation in experimental colitis transcriptionally drives Lnc-UC through direct binding to two κB sites. Lnc-UC ablation disrupts colonic expressions of clock genes in mice; particularly, Rev-erbα is down-regulated and its diurnal rhythm is blunted. Consistently, Lnc-UC promotes expression of Rev-erbα (a known dual NF-κB/Nlrp3 repressor) to inactivate NF-κB signaling and Nlrp3 inflammasome in macrophages. Furthermore, Lnc-UC ablation sensitizes mice to experimental colitis and abolishes the diurnal rhythmicity in disease severity. Mechanistically, Lnc-UC physically interacts with Cbx1 protein to reduce its gene silencing activity via H3K9me3, thereby enhancing Rev-erbα transcription and expression. In addition, we identify a human Lnc-UC that has potential to promote Rev-erbα expression and restrain inflammations.

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Association of Circadian Clock Gene Expression with Glioma Tumor Microenvironment and Patient Survival

Cancers ◽

10.3390/cancers13112756 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2756

Author(s):

Julianie De La Cruz Minyety ◽

Dorela D. Shuboni-Mulligan ◽

Nicole Briceno ◽

Demarrius Young ◽

Mark R. Gilbert ◽

...

Keyword(s):

Gene Expression ◽

Circadian Clock ◽

Clock Gene ◽

Clock Genes ◽

The Cancer Genome Atlas ◽

Lower Grade ◽

Circadian Clock Gene ◽

Clock Gene Expression ◽

Mutational Status ◽

Circadian Clock Genes

Circadian clock genes have been linked to clinical outcomes in cancer, including gliomas. However, these studies have not accounted for established markers that predict the prognosis, including mutations in Isocitrate Dehydrogenase (IDH), which characterize the majority of lower-grade gliomas and secondary high-grade gliomas. To demonstrate the connection between circadian clock genes and glioma outcomes while accounting for the IDH mutational status, we analyzed multiple publicly available gene expression datasets. The unsupervised clustering of 13 clock gene transcriptomic signatures from The Cancer Genome Atlas showed distinct molecular subtypes representing different disease states and showed the differential prognosis of these groups by a Kaplan–Meier analysis. Further analyses of these groups showed that a low period (PER) gene expression was associated with the negative prognosis and enrichment of the immune signaling pathways. These findings prompted the exploration of the relationship between the microenvironment and clock genes in additional datasets. Circadian clock gene expression was found to be differentially expressed across the anatomical tumor location and cell type. Thus, the circadian clock expression is a potential predictive biomarker in glioma, and further mechanistic studies to elucidate the connections between the circadian clock and microenvironment are warranted.

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The BrGI Circadian Clock Gene Is Involved in the Regulation of Glucosinolates in Chinese Cabbage

Genes ◽

10.3390/genes12111664 ◽

2021 ◽

Vol 12 (11) ◽

pp. 1664

Author(s):

Nan-Sun Kim ◽

Su-Jeong Kim ◽

Jung-Su Jo ◽

Jun-Gu Lee ◽

Soo-In Lee ◽

...

Keyword(s):

Transgenic Plants ◽

Circadian Clock ◽

Brassica Rapa ◽

Chinese Cabbage ◽

Clock Gene ◽

Clock Genes ◽

Floral Induction ◽

Stem Elongation ◽

Circadian Clock Gene ◽

Clock System

Circadian clocks integrate environmental cues with endogenous signals to coordinate physiological outputs. Clock genes in plants are involved in many physiological and developmental processes, such as photosynthesis, stomata opening, stem elongation, light signaling, and floral induction. Many Brassicaceae family plants, including Chinese cabbage (Brassica rapa ssp. pekinensis), produce a unique glucosinolate (GSL) secondary metabolite, which enhances plant protection, facilitates the design of functional foods, and has potential medical applications (e.g., as antidiabetic and anticancer agents). The levels of GSLs change diurnally, suggesting a connection to the circadian clock system. We investigated whether circadian clock genes affect the biosynthesis of GSLs in Brassica rapa using RNAi-mediated suppressed transgenic Brassica rapa GIGENTEA homolog (BrGI knockdown; hereafter GK1) Chinese cabbage. GIGANTEA plays an important role in the plant circadian clock system and is related to various developmental and metabolic processes. Using a validated GK1 transgenic line, we performed RNA sequencing and high-performance liquid chromatography analyses. The transcript levels of many GSL pathway genes were significantly altered in GK1 transgenic plants. In addition, GSL contents were substantially reduced in GK1 transgenic plants. We report that the BrGI circadian clock gene is required for the biosynthesis of GSLs in Chinese cabbage plants.

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Cognitive Impairment and Dementia: Gaining Insight through Circadian Clock Gene Pathways

Biomolecules ◽

10.3390/biom11071002 ◽

2021 ◽

Vol 11 (7) ◽

pp. 1002

Author(s):

Kenneth Maiese

Keyword(s):

Circadian Rhythm ◽

Cognitive Impairment ◽

Circadian Clock ◽

Neurodegenerative Disorders ◽

Clock Gene ◽

Clock Genes ◽

Financial Burden ◽

Motor Deficits ◽

Circadian Clock Gene ◽

Age Related

Neurodegenerative disorders affect fifteen percent of the world’s population and pose a significant financial burden to all nations. Cognitive impairment is the seventh leading cause of death throughout the globe. Given the enormous challenges to treat cognitive disorders, such as Alzheimer’s disease, and the inability to markedly limit disease progression, circadian clock gene pathways offer an exciting strategy to address cognitive loss. Alterations in circadian clock genes can result in age-related motor deficits, affect treatment regimens with neurodegenerative disorders, and lead to the onset and progression of dementia. Interestingly, circadian pathways hold an intricate relationship with autophagy, the mechanistic target of rapamycin (mTOR), the silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), mammalian forkhead transcription factors (FoxOs), and the trophic factor erythropoietin. Autophagy induction is necessary to maintain circadian rhythm homeostasis and limit cortical neurodegenerative disease, but requires a fine balance in biological activity to foster proper circadian clock gene regulation that is intimately dependent upon mTOR, SIRT1, FoxOs, and growth factor expression. Circadian rhythm mechanisms offer innovative prospects for the development of new avenues to comprehend the underlying mechanisms of cognitive loss and forge ahead with new therapeutics for dementia that can offer effective clinical treatments.

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