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Review
. 2024 May 16:15:1343030.
doi: 10.3389/fgene.2024.1343030. eCollection 2024.

Histone methylation: at the crossroad between circadian rhythms in transcription and metabolism

Mirna González-Suárez  1 , Lorena Aguilar-Arnal  1
Affiliations
Review

Histone methylation: at the crossroad between circadian rhythms in transcription and metabolism

Mirna González-Suárez et al. Front Genet. .

Abstract

Circadian rhythms, essential 24-hour cycles guiding biological functions, synchronize organisms with daily environmental changes. These rhythms, which are evolutionarily conserved, govern key processes like feeding, sleep, metabolism, body temperature, and endocrine secretion. The central clock, located in the suprachiasmatic nucleus (SCN), orchestrates a hierarchical network, synchronizing subsidiary peripheral clocks. At the cellular level, circadian expression involves transcription factors and epigenetic remodelers, with environmental signals contributing flexibility. Circadian disruption links to diverse diseases, emphasizing the urgency to comprehend the underlying mechanisms. This review explores the communication between the environment and chromatin, focusing on histone post-translational modifications. Special attention is given to the significance of histone methylation in circadian rhythms and metabolic control, highlighting its potential role as a crucial link between metabolism and circadian rhythms. Understanding these molecular intricacies holds promise for preventing and treating complex diseases associated with circadian disruption.

Keywords: chromatin; circadian rhythms; epigenetics; histone methylation; metabolism; transcription.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Mammalian molecular clock. At the core of the molecular clock, CLOCK and BMAL1 form a heterodimer and bind to the E-boxes (orange), activating the transcription of the CCGs (yellow). The negative regulators (period and cryptochrome) are transcribed and translated. Their product represses their own transcription. Another feedback loop, the RORE loop, regulates BMAL1 levels (red). These feedback loops, in coordination with specific transcription factors, regulate the transcription of tissue-specific CCGs and, therefore, the circadian biological process.
FIGURE 2
FIGURE 2
(A) Epigenetic regulators in the molecular clock. During the active phase (day), the binding of CLOCK and BMAL1 is associated with the recruitment of chromatin factors: histone acetyltransferase (blue), histone methyltransferase (violet), histone demethylase (orange), and metabolic enzymes (brown). In the repressive phase (night), other chromatin factors will be associated with the molecular clock: histone deacetylase (green), histone methyltransferase (violet), and histone demethylase (orange). These chromatin factors will raise sequential cycles of active-repressive marks in the histones and generate rhythmic transcription of CCGs. (B) Histone methylation and metabolites. Histone methylation is catalyzed by histone methyltransferase and erased by histone demethylase. HMT uses SAM as a donor of the methyl group, creating SAH. SAM is produced in the one-carbon cycle and can be influenced by nutrients such as methionine, folate, choline, or betaine. The ratio of SAM/SAH shows circadian rhythms. HDM uses α-ketoglutarate or FAD as a cofactor. α-KG is an intermediate of the tricarboxylic acid cycle (TCA) or can be produced by glutamate, a circadian metabolite. FAD is a product of the TCA and is directly influenced by the redox state.
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Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. Research in the LA-A laboratory was supported by grants (PAPIIT IN208022) from Universidad Nacional Autónoma de México (UNAM), Human Frontiers Science Program Young Investigators’ (grant RGY0078/2017), and the National Council of Science and Technology (CONAHCyT) FORDECYT-PRONACES/15758/2020, all to LA-A. MG-S is a doctoral student and thanks the Programa de Doctorado en Ciencias Biomédicas de la Universidad Nacional Autónoma de México, and acknowledges the reception of a PhD fellowship from CONAHCyT (2020-000013-01NACF).

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