Broad chromosomal domains of histone modification patterns in C. elegans

Abstract

Chromatin immunoprecipitation identifies specific interactions between genomic DNA and proteins, advancing our understanding of gene-level and chromosome-level regulation. Based on chromatin immunoprecipitation experiments using validated antibodies, we define the genome-wide distributions of 19 histone modifications, one histone variant, and eight chromatin-associated proteins in Caenorhabditis elegans embryos and L3 larvae. Cluster analysis identified five groups of chromatin marks with shared features: Two groups correlate with gene repression, two with gene activation, and one with the X chromosome. The X chromosome displays numerous unique properties, including enrichment of monomethylated H4K20 and H3K27, which correlate with the different repressive mechanisms that operate in somatic tissues and germ cells, respectively. The data also revealed striking differences in chromatin composition between the autosomes and between chromosome arms and centers. Chromosomes I and III are globally enriched for marks of active genes, consistent with containing more highly expressed genes, compared to chromosomes II, IV, and especially V. Consistent with the absence of cytological heterochromatin and the holocentric nature of C. elegans chromosomes, markers of heterochromatin such as H3K9 methylation are not concentrated at a single region on each chromosome. Instead, H3K9 methylation is enriched on chromosome arms, coincident with zones of elevated meiotic recombination. Active genes in chromosome arms and centers have very similar histone mark distributions, suggesting that active domains in the arms are interspersed with heterochromatin-like structure. These data, which confirm and extend previous studies, allow for in-depth analysis of the organization and deployment of the C. elegans genome during development.

Nucleosome fragility is associated with future transcriptional response to developmental cues and stress in C. elegans

“…We did not observe a correlation between H2A.Z incorporation and nucleosome fragility in C. elegans as measured by our assay. Rather, H2A.Z distribution is strongly biased toward active genes (Whittle et al 2008;Liu et al 2011). This distinction could be due to a divergence in H2A.Z properties between yeast and C. elegans (Zlatanova and Thakar 2008).…”

Crossover Heterogeneity in the Absence of Hotspots inCaenorhabditis elegans

“…elegans Sequencing Consortium 1998;Liu et al 2011). We asked whether the center-arm boundary that we have localized for crossover rate coincides with boundaries defined by DNA sequence and chromatin features.…”

“…In C. elegans, recombination and somatic chromatin are broadly correlated via enrichments or depletions on arms vs. centers (Liu et al 2011; Lui and Colaiácovo 2013). Our data show that H3K9me2, a histone modification previously associated with DSB formation in C. elegans (Reddy and Villeneuve 2004), and signatures of open chromatin (H3K4me2, H3K4me3, H4K8Ac, and H4K16Ac) exhibit no conspicuous changes in distribution across the crossover rate boundary.…”

“…The center and arm regions are defined not by cytology but by recombination rate: gene-dense central clusters emerged from the species' earliest genetic map (Brenner 1974). With the genome sequence (C. elegans Sequencing Consortium 1998), extensive annotation (Gerstein et al 2010), and characterization of chromatin modification (Liu et al 2011), it has become clear that the low-recombination central regions of C. elegans chromosomes are gene dense and enriched for highly expressed genes and markers of open chromatin, while the high-recombination arms are enriched for repetitive sequences, genes with low expression, and markers of closed chromatin. C. elegans chromosomes exhibit nearly complete crossover interference, with elaborate regulatory mechanisms that ensure that each pair of chromosomes receives exactly one crossover per meiosis (Hillers and Villeneuve 2003;Hammarlund et al 2005).…”

Epigenetic landscape and miRNA involvement during neural crest development

“…Methylation of certain residues of Histone 3 and combinations of thereof, are involved in the recruitment of various modifiers of chromatin and transcriptional activators or repressor, resulting in different effects on gene expression (Kouzarides, 2007). The trimethylation of H3K4 (H3K4me3), catalyzed by histone methyltranferases of the Trithorax group (TrxG) proteins, is associated with active transcription (Barski et al, 2007;Pan et al, 2007;Cheung et al, 2010); while trimethylation of H3K27 (H3K27me3), established by Polycomb group (PcG) proteins, is associated with transcriptional repression (Schwartz et al, 2006;Tolhuis et al, 2006;Liu et al, 2011). Similarly to H3K4me3, trimethylated H3 lysine 36 (H3K36me3) is also frequently located in transcriptionally active euchromatic regions, with the first predominantly found in the promoter and the second in the bodies of genes.…”