DNA Methylation Targeting: The DNMT/HMT Crosstalk Challenge

Biomolecules. 2017 Jan 5;7(1):3. doi: 10.3390/biom7010003.

Abstract

Chromatin can adopt a decondensed state linked to gene transcription (euchromatin) and a condensed state linked to transcriptional repression (heterochromatin). These states are controlled by epigenetic modulators that are active on either the DNA or the histones and are tightly associated to each other. Methylation of both DNA and histones is involved in either the activation or silencing of genes and their crosstalk. Since DNA/histone methylation patterns are altered in cancers, molecules that target these modifications are interesting therapeutic tools. We present herein a vast panel of DNA methyltransferase inhibitors classified according to their mechanism, as well as selected histone methyltransferase inhibitors sharing a common mode of action.

Keywords: DNA methylation; DNMT inhibitors; DNMT/HMT crosstalk; HMT inhibitors; histone methylation.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Chromatin / genetics
  • Chromatin / metabolism
  • Clinical Trials as Topic
  • DNA (Cytosine-5-)-Methyltransferases / antagonists & inhibitors
  • DNA (Cytosine-5-)-Methyltransferases / metabolism
  • DNA Methylation* / drug effects
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use*
  • Epigenesis, Genetic / drug effects
  • Gene Silencing
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase / antagonists & inhibitors
  • Histone-Lysine N-Methyltransferase / metabolism
  • Histones / metabolism
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology
  • Neoplasms / genetics

Substances

  • Antineoplastic Agents
  • Chromatin
  • Enzyme Inhibitors
  • Histones
  • Histone Methyltransferases
  • DNA (Cytosine-5-)-Methyltransferases
  • Histone-Lysine N-Methyltransferase