Post-translational histone modifications associated with the development of metabolic dysfunction-associated fatty liver disease. Part 1. General provisions

Abstract

Based on the analysis of literary sources of PubMed, MedLine, The Cochrane Library, EMBASE database, the authors of the article give general provisions regarding post-translational modifications of histones (small proteins with a molecular weight of 10–15 kDa, which make up the largest part of nuclear proteins), which are associated with the development of metabolic dysfunction-associated fatty liver disease. The authors emphasize that post-translational histone modifications regulate the activity of gene expression, and each of these types differently changes the structure of chromatin and, as a result, gene expression. Currently, more than 20 types of histone protein modifications have been identified (acetylation, biotinylation, butyrylation, 2-hydroxybutyrylation, ADP-ribosylation, N-formylation, hydroxylation, glycosylation, glutarylation, dopaminylation, proline isomerization and aspartic acid carbonylation, crotonylation, lactylation, malonylation, methylation, propionylation, succinylation, SUMOylation, ubiquitination, phosphorylation, citrullination). Epigenetic and epitranscriptomic changes are induced by lifestyle, especially the nature of diet and physical activity, by the influence of exogenous and endogenous factors. Prolonged epigenetic changes that determine the expression of target genes can be accompanied by the development of metabolic disorders and the progression of metabolic dysfunction-associated fatty liver disease. Histone modification is carried out by site-specific enzymes: writers, which identify a marker, and erasers, which “erase” a marker. Post-translational histone modifications change the local physicochemical environment and, based on this, directly affect the structure of the nucleosome and chromatin. Also, post-translational modifications of the N- and C-terminal tails of histone proteins act as “docking sites” that recruit specific molecular readers. Readers of histone modifications can act both in the intranucleosomal space, modifying adjacent histone sites or recruiting transcription factors, transcription activators and repressors, and in the internucleosomal space. The authors also describe the pathophysiological significance of post-translational histone modifications in the development of metabolic dysfunction-associated fatty liver disease, the diagnostic value of epigenetic biomarkers, and the potential of pharmacological management of histone modifications to achieve inhibition of the activity of the pathological process.