Histone Deacetylase 9: Its Role in the Pathogenesis of Diabetes and Other Chronic Diseases

Diabetes Metab J. 2020 Apr;44(2):234-244. doi: 10.4093/dmj.2019.0243.

Abstract

As a member of the class IIa histone deacetylases (HDACs), HDAC9 catalyzes the deacetylation of histones and transcription factors, commonly leading to the suppression of gene transcription. The activity of HDAC9 is regulated transcriptionally and post-translationally. HDAC9 is known to play an essential role in regulating myocyte and adipocyte differentiation and cardiac muscle development. Also, recent studies have suggested that HDAC9 is involved in the pathogenesis of chronic diseases, including cardiovascular diseases, osteoporosis, autoimmune disease, cancer, obesity, insulin resistance, and liver fibrosis. HDAC9 modulates the expression of genes related to the pathogenesis of chronic diseases by altering chromatin structure in their promotor region or reducing the transcriptional activity of their respective transcription factors. This review summarizes the current knowledge of the regulation of HDAC9 expression and activity. Also, the roles of HDAC9 in the pathogenesis of chronic diseases are discussed, along with potential underlying mechanisms.

Keywords: Autoimmune diseases; Cardiovascular diseases; Chronic disease; Epigenomics; Histone deacetylases; Neoplasms; Obesity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Adipocytes / metabolism
  • Adipocytes / pathology
  • Animals
  • Autoimmune Diseases / metabolism
  • Autoimmune Diseases / physiopathology
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / physiopathology
  • Cell Differentiation
  • Chronic Disease
  • Diabetes Mellitus / metabolism*
  • Diabetes Mellitus / physiopathology
  • Female
  • Histone Deacetylases / genetics*
  • Histones / metabolism*
  • Humans
  • Insulin Resistance / genetics
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis / physiopathology
  • Mice
  • Muscle Cells / metabolism
  • Muscle Cells / pathology
  • Neoplasms / metabolism
  • Neoplasms / physiopathology
  • Obesity / metabolism
  • Obesity / physiopathology
  • Osteoporosis / metabolism
  • Osteoporosis / physiopathology
  • Polymorphism, Single Nucleotide / genetics
  • Promoter Regions, Genetic / genetics
  • Repressor Proteins / genetics*
  • Transcription Factors / metabolism*

Substances

  • Histones
  • Repressor Proteins
  • Transcription Factors
  • HDAC9 protein, human
  • Histone Deacetylases