Discovering the Physiological Significance and Regulatory Mechanisms of Circadian Rhythm Generation

Dear Colleagues,

Internal biological clocks govern the timing of various physiological processes to generate circadian rhythms and are essential to the regulation of numerous aspects of an organism's life. These rhythms are crucial for coordinating various cellular functions, including metabolism, hormone secretion, immune response, and behavior, in alignment with the external day–night cycle.

In recent years, significant research progress has been made regarding the regulation of circadian gene expression rhythms. Circadian rhythms interact closely with various cellular functions in different cell types, thus requiring their operation to possess plasticity and specificity in different environments. Gene expression regulation involves multiple mechanisms at the transcriptional level (such as transcription factors, and many cofactors involved in histone modification and chromatin remodeling), as well as mechanisms at the post-transcriptional and metabolite levels, making it highly complex. How these mechanisms participate in the regulation of circadian rhythms awaits future research at the genomic scale, with their physiological significance also worthy of exploration.

This Special Issue aims to present recent advances and ongoing research on this topic in different species. It welcomes the submission of original research and review articles focusing on the regulatory mechanisms of circadian rhythms and their physiological significance.

Dr. Xiaodong Li
Guest Editor

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• circadian rhythms
• biological clocks
• chromatin
• transcription
• histone
• nucleosome
• pausing
• pause release

Title: H3.3K27M regulates the Drosophila circadian clock by inhibiting the transcription of period
Authors: Shujing Li 1, 2; Qingqing Wang 1; Shuning Zhou 1; Huaifeng Liu 1; Xianggang Wang 1; Mengna Li 1,2; Yu Gao 1,3,*
Affiliation: 1 School of Life Science, Bengbu Medical College, Bengbu, Anhui, China. 2 Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China. 3 Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical College, Bengbu, China.
Abstract: Circadian rhythms, found in almost all living things on Earth, are thought to be driven by endogenous molecular clocks composed of clock-controlled genes (CCGs). The expressions of CCGs are regulated by epigenetic modifications, but the underlying mechanisms have not been fully elucidated. In this study, the overexpressing H3.3K27M (Lysine to Methionine mutations at position 27 in the histone H3.3) in Drosophila neurons and glial cells was identified with enough to lengthen the period of the Drosophila locomotor rhythm. The overexpression of H3.3K27M could reduce the mRNA level of the core circadian gene period (per). Consistently, overexpressing H3.3K27M in human glioma cells could reduce the Period1 (Per1) mRNA level. Meanwhile, RNA-seq results showed overexpression of H3.3K27M could lead to 257 significantly upregulated and 235 significantly downregulated differentially expressed genes at CT 12 time point (also the peak time point of per expression). In addition to the circadian rhythm pathway, the differentially expressed genes were significantly enriched in Toll and Imd signaling pathway. Thus, the result suggested that H3.3K27M regulates the Drosophila circadian clock by inhibiting the transcription of per，and also affects the expression of circadian genes in the Toll and Imd signaling pathway.

Title: The Transcriptional Regulation of Circadian Rhythm in Mammals
Authors: Wei Mao *,1,2,3, Qianping Chen 1,2,3, Jia-Da Li 4
Affiliation: 1 The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou 310000, Zhejiang, China. 2 Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang 310000, China. 3 Zhejiang Key Laboratory of Radiation Oncology, Hangzhou 310000, China. 4 Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
Abstract: All organisms, from the simplest unicellular bacteria to advanced mammals, have a near 24-hour circadian rhythm. Circadian rhythms are highly conserved across different life forms and are regulated by circadian genes as well as by related transcription factors. The role of transcription factors underlies circadian rhythms, regulating gene expression, plant and animal behavior, and even human disease. In this review, we focus on the research basis for transcriptional regulation of circadian rhythms, with particular attention to histone modifications, chromatin remodeling, and Pol II pausing control in transcriptional regulation. These studies have advanced our understanding of transcriptional regulation in biological circadian rhythms and advanced the understanding of the importance of circadian biology to human health. Finally, we summarize the progress and challenges in these three areas of regulation to move the field forward.