Understanding the interplay between CpG island-associated gene promoters and H3K4 methylation

Biochim Biophys Acta Gene Regul Mech. 2020 Aug;1863(8):194567. doi: 10.1016/j.bbagrm.2020.194567. Epub 2020 Apr 29.

Abstract

The precise regulation of gene transcription is required to establish and maintain cell type-specific gene expression programs during multicellular development. In addition to transcription factors, chromatin, and its chemical modification, play a central role in regulating gene expression. In vertebrates, DNA is pervasively methylated at CG dinucleotides, a modification that is repressive to transcription. However, approximately 70% of vertebrate gene promoters are associated with DNA elements called CpG islands (CGIs) that are refractory to DNA methylation. CGIs integrate the activity of a range of chromatin-regulating factors that can post-translationally modify histones and modulate gene expression. This is exemplified by the trimethylation of histone H3 at lysine 4 (H3K4me3), which is enriched at CGI-associated gene promoters and correlates with transcriptional activity. Through studying H3K4me3 at CGIs it has become clear that CGIs shape the distribution of H3K4me3 and, in turn, H3K4me3 influences the chromatin landscape at CGIs. Here we will discuss our understanding of the emerging relationship between CGIs, H3K4me3, and gene expression.

Keywords: Chromatin; CpG islands; DNA methylation; H3K4me3; Transcription.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Chromatin
  • CpG Islands / genetics*
  • DNA Methylation
  • DNA-Binding Proteins
  • Gene Expression Regulation
  • Histone-Lysine N-Methyltransferase
  • Histones / genetics*
  • Histones / metabolism*
  • Myeloid-Lymphoid Leukemia Protein
  • Neoplasm Proteins
  • Promoter Regions, Genetic*
  • Protein Processing, Post-Translational*
  • Transcription, Genetic

Substances

  • Chromatin
  • DNA-Binding Proteins
  • Histones
  • KMT2D protein, human
  • Neoplasm Proteins
  • histone H3 trimethyl Lys4
  • Myeloid-Lymphoid Leukemia Protein
  • Histone-Lysine N-Methyltransferase