Proceedings of the International scientific and practical conference ―New York Global Science Conference 2026‖ (March 6-8, 2026) / Publisher website: www.naukainfo.com. – New York, USA, 2026. - 250 p.

202 Notably, increased expression of nuclear receptor subfamily 2 group F member 6 has been observed in liver tissue from patients with MASLD, whereas metformin administration in obese mouse models resulted in suppression of NR2F6 expression. These findings suggest that pharmacological inhibition of NR2F6 could represent a potential therapeutic strategy for MASLD, possibly mediated through mechanisms involving histone acetylation [8]. Histone acetylation is also capable of regulating the transcriptional activity of multiple genes simultaneously. For instance, experimental models carrying a homozygous knock-in mutation involving substitution of serine with alanine at the phospho-Caspase-9 site of liver X receptor alpha demonstrated the development of hepatic steatosis while simultaneously preventing excessive cholesterol accumulation, inflammation, and fibrotic remodeling. Such molecular alterations were associated with a delayed progression from simple hepatic steatosis to MASH [9]. In addition to acetylation and methylation, other post-translational histone alteration have recently attracted increasing attention. Ubiquitination, defined as the covalent attachment of ubiquitin molecules to specific residues of target proteins, and sumoylation, which involves conjugation of small ubiquitin-like modifier proteins to substrates, represent additional regulatory mechanisms of chromatin function. Accumulating evidence indicates that post-translational modification of transcription factors during protein maturation plays a crucial role in the regulation of numerous cellular and metabolic processes [10]. An analysis of hepatic gene expression networks in obese individuals with MASLD demonstrated that signaling pathways associated with hepatic fibrosis were predominantly enriched within the group of upregulated genes, whereas pathways related to endoplasmic reticulum stress and protein ubiquitination were among the most significantly suppressed gene clusters. Beyond ubiquitination, transcription factors may undergo a variety of additional post-translational alterations, including acetylation, phosphorylation, and glycosylation. However, the precise contribution of these regulatory mechanisms to