Sharing Marks: H3K4 Methylation and H2B Ubiquitination as Features of Meiotic Recombination and Transcription

Int J Mol Sci. 2020 Jun 25;21(12):4510. doi: 10.3390/ijms21124510.

Abstract

Meiosis is a specialized cell division that gives raise to four haploid gametes from a single diploid cell. During meiosis, homologous recombination is crucial to ensure genetic diversity and guarantee accurate chromosome segregation. Both the formation of programmed meiotic DNA double-strand breaks (DSBs) and their repair using homologous chromosomes are essential and highly regulated pathways. Similar to other processes that take place in the context of chromatin, histone posttranslational modifications (PTMs) constitute one of the major mechanisms to regulate meiotic recombination. In this review, we focus on specific PTMs occurring in histone tails as driving forces of different molecular events, including meiotic recombination and transcription. In particular, we concentrate on the influence of H3K4me3, H2BK123ub, and their corresponding molecular machineries that write, read, and erase these histone marks. The Spp1 subunit within the Complex of Proteins Associated with Set1 (COMPASS) is a critical regulator of H3K4me3-dependent meiotic DSB formation. On the other hand, the PAF1c (RNA polymerase II associated factor 1 complex) drives the ubiquitination of H2BK123 by Rad6-Bre1. We also discuss emerging evidence obtained by cryo-electron microscopy (EM) structure determination that has provided new insights into how the "cross-talk" between these two marks is accomplished.

Keywords: COMPASS; DSB; PAF1c; histone; meiosis; methylation; recombination; transcription; ubiquitination.

Publication types

  • Review

MeSH terms

  • Animals
  • Chromatin / metabolism
  • Chromosomes / metabolism
  • DNA Breaks, Double-Stranded
  • DNA-Binding Proteins / metabolism
  • Endodeoxyribonucleases
  • Histone-Lysine N-Methyltransferase
  • Histones / genetics*
  • Histones / metabolism
  • Homologous Recombination / genetics
  • Homologous Recombination / physiology*
  • Humans
  • Meiosis / genetics
  • Meiosis / physiology*
  • Methylation
  • Protein Processing, Post-Translational / genetics
  • Ubiquitin-Conjugating Enzymes / genetics
  • Ubiquitination

Substances

  • Chromatin
  • DNA-Binding Proteins
  • Histones
  • histone H3 trimethyl Lys4
  • Histone-Lysine N-Methyltransferase
  • Ubiquitin-Conjugating Enzymes
  • Endodeoxyribonucleases