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National Institute on Alcohol Abuse and Alcoholism/NIH

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Pharmacol. Ther. , Oct 12 2023, S0163-7258(23)00211-5 | https://doi.org/10.1016/j.pharmthera.2023.108547 Post-translational modifications of histone and non-histone proteins in epigenetic regulation and translational applications in alcohol-associated liver disease: Challenges and research opportunities.

Wiramon Rungratanawanich ^a, Jacob W. Ballway ^a, Xin Wang ^b, Kyoung-Jae Won ^c, James P. Hardwick ^d, Byoung-Joon Song ^a

^aSection of Molecular Pharmacology and Toxicology, National Institute on Alcohol Abuse and Alcoholism, 9000 Rockville Pike, Bethesda, MD 20892, USA

^bDepartment of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA

^cDepartment of Computational Biomedicine, Cedars-Sinai Medical Center, West Hollywood, CA, 90069, USA

^dDepartment of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, OH 44272, USA

Corresponding authors : James P. Hardwick, Byoung-Joon Song

Abstract

Epigenetic regulation is a process that takes place through adaptive cellular pathways influenced by environmental factors and metabolic changes to modulate gene activity with heritable phenotypic variations without altering the DNA sequences of many target genes. Epigenetic regulation can be facilitated by diverse mechanisms: many different types of post-translational modifications (PTMs) of histone and non-histone nuclear proteins, DNA methylation, altered levels of noncoding RNAs, incorporation of histone variants, nucleosomal positioning, chromatin remodeling, etc. These factors modulate chromatin structure and stability with or without the involvement of metabolic products, depending on the cellular context of target cells or environmental stimuli, such as intake of alcohol (ethanol) or Western-style high-fat diets. Alterations of epigenetics have been actively studied, since they are frequently associated with multiple disease states. Consequently, explorations of epigenetic regulation have recently shed light on the pathogenesis and progression of alcohol-associated disorders. In this review, we highlight the roles of various types of PTMs, including less-characterized modifications of nuclear histone and non-histone proteins, in the epigenetic regulation of alcohol-associated liver disease (ALD) and other disorders. We also describe challenges in characterizing specific PTMs and suggest future opportunities for basic and translational research to prevent or treat ALD and many other disease states.

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형식Review Paper
게재일2023년 10월 (BRIC 등록일 2023-10-24)
연구진국외 연구진
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