Histone methylation sets the stage for meiotic DNA breaks

Abstract

Covalent post-translational modifications of histones have important functions in transcription, replication, repair, and other aspects of eukaryotic chromosome dynamics. Trimethylation of lysine-4 on histone H3 is enriched at actively transcribed loci in many organisms. The impact of this histone modification on transcription has been extensively studied, but less is known about its effects on other chromosomal processes. An intriguing new study in this issue of EMBO Journal demonstrates that H3 lysine-4 trimethylation is critical in budding yeast for formation of the programmed DNA double-strand breaks that initiate homologous recombination during meiosis. These findings have important implications for elucidating the previously recognized but little understood connections between meiotic break formation and transcriptional promoters in this organism.

Figure 1

Integration of multiple histone modifications promotes the formation of meiotic DSBs. It is likely that a combination of histone modifications is established at promoter regions prior to entry into meiosis. Ubiquitination of lysine-123 of H2B promotes subsequent Set1 activity upon lysine-4 of H3. H3K4^me3 is then read by a putative trimethyl-lysine reader either contained as part of the pol II machinery or as a component of the DSB protein complex allowing for the formation of the majority of DSBs within promoters. Other subsets of DSBs occur within alternative chromatin environments and occur within ORFs, intergenic, and heterochromatic regions. Frequencies of meiotic DSBs are depicted by a smoothed histogram along a fictitious segment of yeast chromosome. Purple shading signifies promoters with nucleosomes enriched with the combination of H2B^ub and H3K4^me3, whereas ORFs are indicated by blue arrows.