Histone deacetylase‑2: A potential regulator and therapeutic target in liver disease (Review)

Abstract

Histone acetyltransferases are responsible for histone acetylation, while histone deacetylases (HdAcs) counteract histone acetylation. An unbalanced dynamic between histone acetylation and deacetylation may lead to aberrant chromatin landscape and chromosomal function. HdAc2, a member of class I HdAc family, serves a crucial role in the modulation of cell signaling, immune response and gene expression. HdAc2 has emerged as a promising therapeutic target for liver disease by regulating gene transcription, chromatin remodeling, signal transduction and nuclear reprogramming, thus receiving attention from researchers and clinicians. The present review introduces biological information of HdAc2 and its physiological and biochemical functions. Secondly, the functional roles of HdAc2 in liver disease are discussed in terms of hepatocyte apoptosis and proliferation, liver regeneration, hepatocellular carcinoma, liver fibrosis and non-alcoholic steatohepatitis. Moreover, abnormal expression of HdAc2 may be involved in the pathogenesis of liver disease, and its expression levels and pharmacological activity may represent potential biomarkers of liver disease. Finally, research on selective HdAc2 inhibitors and non-coding RNAs relevant to HdAc2 expression in liver disease is also reviewed. The aim of the present review was to improve understanding of the multifunctional role and potential regulatory mechanism of HdAc2 in liver disease.

Hyperlipidemia May Synergize with Hypomethylation in Establishing Trained Immunity and Promoting Inflammation in NASH and NAFLD

“…Furthermore, increased histone acetylation by inhibiting histone deacetylase-2 (HDAC2) promotes macrophage infiltration and progression of NASH [ 110 ]. MAT1A and GNMT are relatively liver-specific enzymes; hypomethylation in the liver of MAT1A-KO and GNMT-KO can be striking.…”

Roles and regulation of histone acetylation in hepatocellular carcinoma

“…Over the past decades, the development of epigenetics (e.g., microRNA, DNA methylation, and histone modification) has provided a fresh view to uncover the mechanisms of liver carcinogenesis ( Bayo et al, 2019 ; Ganai, 2020b ; Liu et al, 2021 ). Epigenetic phenomena refer to heritable adaptive reversible changes in gene expression that are not induced by changes in the DNA sequence ( Cavalli and Heard, 2019 ).…”

Histone Modifications and Non-Coding RNAs: Mutual Epigenetic Regulation and Role in Pathogenesis

“…As a result, the bonds between DNA and histones are weakened following chromatin decondensation and transcription activation [ 193 ]. Histone proteins have structural and functional roles almost in all nuclear processes, and its aberrations are associated with such diseases as tumors, liver injury, viral hepatitis and Alzheimer’s disease [ 23 , 194 ].…”