Differential Expression of SWI/SNF Chromatin Remodeler Subunits Brahma and Brahma-Related Gene During Drug-Induced Liver Injury and Regeneration in Mouse Model

DNA Cell Biol. 2016 Aug;35(8):373-84. doi: 10.1089/dna.2015.3155. Epub 2016 Apr 20.

Abstract

The chromatin remodeling activity of mammalian SWI/SNF complex is carried out by either Brahma (BRM) or Brahma-related gene (BRG-1). The BRG-1 regulates genes involved in cell proliferation, whereas BRM is associated with cell differentiation, and arrest of cell growth. Global modifications of histones and expression of genes of chromatin-remodeling subunits have not been studied in in vivo model systems. In the present study, we investigate epigenetic modifications of histones and the expression of genes in thioacetamide (TAA)-induced liver injury and regeneration in a mouse model. In the present study, we report that hepatocyte proliferation and H3S10 phosphorylation occur during 60 to 72 h post TAA treatment in mice. Furthermore, there was change in the H3K9 acetylation and H3K9 trimethylation pattern with respect to liver injury and regeneration phase. Looking into the expression pattern of Brg-1 and Brm, it is evident that they contribute substantially to the process of liver regeneration. The SWI/SNF remodeler might contain BRG-1 as its ATPase subunit during injury phase. Whereas, BRM-associated SWI/SNF remodeler might probably be predominant during decline of injury phase and initiation of regeneration phase. Furthermore, during the regeneration phase, BRG-1-containing remodeler again predominates. Considering all these observations, the present study depicts an interplay between chromatin interacting machineries in different phases of thioacetamide-induced liver injury and regeneration.

MeSH terms

  • Animals
  • Cell Cycle / genetics
  • Cell Differentiation
  • Cell Proliferation
  • Chemical and Drug Induced Liver Injury / etiology
  • Chemical and Drug Induced Liver Injury / genetics*
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / rehabilitation
  • Chromatin / chemistry
  • Chromatin / metabolism
  • Chromatin Assembly and Disassembly*
  • Chromosomal Proteins, Non-Histone / genetics*
  • Chromosomal Proteins, Non-Histone / metabolism
  • DNA Helicases / genetics*
  • DNA Helicases / metabolism
  • Epigenesis, Genetic*
  • Female
  • Hepatocytes / metabolism
  • Hepatocytes / pathology
  • Histones / genetics
  • Histones / metabolism
  • Liver / injuries
  • Liver / metabolism
  • Liver Regeneration / genetics*
  • Mice
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Phosphorylation
  • Signal Transduction
  • Thioacetamide / toxicity
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism

Substances

  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • Histones
  • Nuclear Proteins
  • SWI-SNF-B chromatin-remodeling complex
  • Smarca2 protein, mouse
  • Transcription Factors
  • Thioacetamide
  • Smarca4 protein, mouse
  • DNA Helicases