Replication and active demethylation represent partially overlapping mechanisms for erasure of H3K4me3 in budding yeast.
Histone modifications affect DNA-templated processes ranging from transcription to genomic replication. In this study, we examine the cell cycle dynamics of the trimethylated form of histone H3 lysine 4 (H3K4me3), a mark of active chromatin that is viewed as "long-lived" and that is involved in memory during cell state inheritance in metazoans. We synchronized yeast using two different protocols, then followed H3K4me3 patterns as yeast passed through subsequent cell cycles. While most H3K4me3 patterns were conserved from one generation to the next, we found that methylation patterns induced by alpha factor or high temperature were erased within one cell cycle, during S phase. Early-replicating regions were erased before late-replicating regions, implicating replication in H3K4me3 loss. However, nearly complete H3K4me3 erasure occurred at the majority of loci even when replication was prevented, suggesting that most erasure results from an active process. Indeed, deletion of the demethylase Jhd2 slowed erasure at most loci. Together, these results indicate overlapping roles for passive dilution and active enzymatic demethylation in erasing ancestral histone methylation states in yeast.
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
Marta
M
Radman-Livaja
Chih Long
CL
Liu
Nir
N
Friedman
Stuart L
SL
Schreiber
Oliver J
OJ
Rando
D004261:DNA Replication; D016681:Genome, Fungal / Q000235:genetics; D006657:Histones / Q000378:metabolism*; D056484:Jumonji Domain-Containing Histone Demethylases / Q000378:metabolism; D007700:Kinetics; D008239:Lysine; D000072235:Mating Factor; D008745:Methylation; D009707:Nucleosomes / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D016196:S Phase; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D013696:Temperature
D006657:Histones; D009707:Nucleosomes; D010455:Peptides; D029701:Saccharomyces cerevisiae Proteins; D000072235:Mating Factor; C519119:JHD2 protein, S cerevisiae; D056484:Jumonji Domain-Containing Histone Demethylases; D008239:Lysine