A nucleosome turnover map reveals that the stability of histone H4 Lys20 methylation depends on histone recycling in transcribed chromatin

Abstract

Nucleosome composition actively contributes to chromatin structure and accessibility. Cells have developed mechanisms to remove or recycle histones, generating a landscape of differentially aged nucleosomes. This study aimed to create a highresolution, genome-wide map of nucleosome turnover in Schizosaccharomyces pombe. The recombination-induced tag exchange (RITE) method was used to study replication-independent nucleosome turnover through the appearance of new histone H3 and the disappearance or preservation of old histone H3. The genome-wide location of histones was determined by chromatin immunoprecipitation-exonuclease methodology (ChIP-exo). The findings were compared with diverse chromatin marks, including histone variant H2A.Z, post-translational histone modifications, and Pol II binding. Finally, genomewide mapping of the methylation states of H4K20 was performed to determine the relationship between methylation (mono, di, and tri) of this residue and nucleosome turnover. Our analysis showed that histone recycling resulted in low nucleosome turnover in the coding regions of active genes, stably expressed at intermediate levels. High levels of transcription resulted in the incorporation of new histones primarily at the end of transcribed units. H4K20 was methylated in lowturnover nucleosomes in euchromatic regions, notably in the coding regions of long genes that were expressed at low levels. This transcription-dependent accumulation of histone methylation was dependent on the histone chaperone complex FACT. Our data showed that nucleosome turnover is highly dynamic in the genome and that several mechanisms are at play to either maintain or suppress stability. In particular, we found that FACT-associated transcription conserves histones by recycling them and is required for progressive H4K20 methylation.

Understanding nucleosome dynamics and their links to gene expression and DNA replication

“…Exchange is even more rapid when transcription is occurring in these regions. Similar turnover studies have been conducted in flies, mice and humans, including expanded studies to monitor turnover of histone variants 62–65 , as well as the turnover rates of PTMs 66 . Together, these studies have revealed that genomic regions with the highest rates of nucleosome (and histone) turnover are biochemically active.…”

Non-coding RNA-mediated epigenetic regulation of liver fibrosis

“…Histone modifications serve the role of allotting the genome into "active" or euchromatin, in which DNA is accessible for transcription, and "inactive" or heterochromatin, in which DNA is inaccessible for transcription [94]. Histones are characterized by their large number and diversity of modified residues [95].…”

Fission yeast meets a legend in Kobe: report of the Eighth International Fission Yeast Meeting

“…H3K9 methylation decreased after the release of the methyltransferase in the wild type but was maintained across generations and postmeiosis in a deletion mutant of the lysine demethylase Epe1 . Peter Svensson (Karolinska Institute, Sweden) described the genomewide nucleosome turnover based on the recombination-induced tag exchange (RITE) method adapted for S. pombe in collaboration with Allshire's group; accordingly, he showed low and high nucleosome turnover in heterochromatin and high-expression chromatin regions, respectively (Svensson et al 2015). Shiv Grewal (National Institutes of Health, USA) presented findings from his group's genomewide chromatin conformation capture (Hi-C) analysis (Mizuguchi et al 2014).…”