Trichostatin A decreases the levels of MeCP2 expression and phosphorylation and increases its chromatin binding affinity

Epigenetics. 2017;12(11):934-944. doi: 10.1080/15592294.2017.1380760. Epub 2017 Dec 5.

Abstract

MeCP2 binds to methylated DNA in a chromatin context and has an important role in cancer and brain development and function. Histone deacetylase (HDAC) inhibitors are currently being used to palliate many cancer and neurological disorders. Yet, the molecular mechanisms involved are not well known for the most part and, in particular, the relationship between histone acetylation and MeCP2 is not well understood. In this paper, we study the effect of the HDAC inhibitor trichostatin A (TSA) on MeCP2, a protein whose dysregulation plays an important role in these diseases. We find that treatment of cells with TSA decreases the phosphorylation state of this protein and appears to result in a higher MeCP2 chromatin binding affinity. Yet, the binding dynamics with which the protein binds to DNA appear not to be significantly affected despite the chromatin reorganization resulting from the high levels of acetylation. HDAC inhibition also results in an overall decrease in MeCP2 levels of different cell lines. Moreover, we show that miR132 increases upon TSA treatment, and is one of the players involved in the observed downregulation of MeCP2.

Keywords: MeCP2; Trichostatin A (TSA); chromatin; histone acetylation; miR-132.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Chromatin / metabolism*
  • HEK293 Cells
  • HeLa Cells
  • Histone Deacetylase Inhibitors / pharmacology*
  • Humans
  • Hydroxamic Acids / pharmacology*
  • Methyl-CpG-Binding Protein 2 / genetics*
  • Methyl-CpG-Binding Protein 2 / metabolism
  • Mice
  • Phosphorylation
  • Protein Binding / drug effects
  • Protein Processing, Post-Translational / drug effects*

Substances

  • Chromatin
  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • MECP2 protein, human
  • Methyl-CpG-Binding Protein 2
  • trichostatin A

Grants and funding