Clock Genes and Their Regulation

Introduction of Clock Genes

Clock genes (CGs) are important parts of the circadian clock for the generation of gene expression oscillations. The central circadian clock exerts control of multiple aspects of human physiology, such as sleep, metabolism, and the immune system. What’s more, recent studies have shown that the circadian clock also plays an important role in controlling the cardiovascular and nervous system, intestinal microbiota, aging, and cancer.

In recent years, some studies have shown that clock genes are closely related to neuronal function and disease. For example, single nucleotide mutation in NPAS2, NR1D1, and PER1 is linked to the cause of autism spectrum disorder. The reduced expression of CLOCK protein has been detected in epileptogenic tissues. In the patients with major depressive disorder (MDD), it has been found that the rhythmicity of CGs like BMAL1, BHLHE40-41, DBP, NR1D1, and PER1-2-3 was disrupted. As an activator of downstream elements, the CLOCK protein plays an important role in the pathway critical to the generation of the circadian rhythm. The CLOCK protein has been shown to affect the migration of neuronal cells.

Research for Clock Genes

The development and function of the human brain are maintained by embryonic and adult neurogenesis, studies have shown the involvement of CGs in neurogenesis. According to the genetic manipulation of interested CGs, the role of CGs in the nervous system can be discovered clearly. According to the analysis of scRNA-seq datasets of embryonic and adult neurogenic niches, the cell type identity and expression dynamics of CGs can be explored. As most of the CGs function as transcription factors (TFs) with a series of genomic targets, it is necessary to establish the co-expression networks (CNs).

Recent studies showed that the abnormal expression of clock genes has been found in multiple abdominal malignant tumors, including colorectal, liver, gastric, and pancreatic cancer. In addition, their abnormal expression is closely associated with clinical tumor parameters or patient prognosis. In this case, the clock genes research may expand the understanding of tumor occurrence and development mechanism, as well as provide novel approaches for tumor treatment.

Fig.1 Representation of the circadian clock network. (Yang, 2017)

Research Methods for Circadian Clock

• Pseudotime analysis
• Co-expression analysis
• ScRNA-seq dataset description

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Reference

1. Yang, S.; et al. Research progress on circadian clock genes in common abdominal malignant tumors. Oncology letters. 2017, 14(5): 5091-5098.