Evolution of H3K27me3-marked chromatin is linked to gene expression evolution and to patterns of gene duplication and diversification

Abstract

Histone modifications are critical for the regulation of gene expression, cell type specification, and differentiation. However, evolutionary patterns of key modifications that regulate gene expression in differentiating organisms have not been examined. Here we mapped the genomic locations of the repressive mark histone 3 lysine 27 trimethylation (H3K27me3) in four species of Drosophila, and compared these patterns to those in C. elegans. We found that patterns of H3K27me3 are highly conserved across species, but conservation is substantially weaker among duplicated genes. We further discovered that retropositions are associated with greater evolutionary changes in H3K27me3 and gene expression than tandem duplications, indicating that local chromatin constraints influence duplicated gene evolution. These changes are also associated with concomitant evolution of gene expression. Our findings reveal the strong conservation of genomic architecture governed by an epigenetic mark across distantly related species and the importance of gene duplication in generating novel H3K27me3 profiles.[Supplemental material is available for this article.]While transcriptional regulation has long been recognized as a significant target of evolutionary change (King and Wilson 1975), the specific mechanisms behind regulatory divergence have been difficult to dissect (Carroll 2008). In most cases, research has focused on recognizable cis-elements where transcription factors bind in a sequence-specific manner (Borneman et al. 2007;Bradley et al. 2010;Dowell 2010;Ni et al. 2012). Changes to either a transcription factor's DNA-binding properties or transcription factor binding sites (TFBS) enable the evolution of differential regulation, and numerous examples of this phenomenon have been observed (Ludwig et al. 2005;Shultzaberger et al. 2012).Whereas changes in cis-regulatory elements have been implicated in phenotypic and specifically morphological changes (Carroll 2008;Stern and Orgogozo 2008), other components of transcriptional regulation such as the chromatin environment have been scarcely explored (Lenhard et al. 2012). Histone modifications, which are chemical alterations of the histone spools upon which DNA is threaded, constitute one of the best-described elements of chromatin state (Zhou et al. 2011). These modifications can act directly or indirectly (through recruited enzymes) to alter DNA accessibility, thereby controlling other DNA-protein interactions (Campos and Reinberg 2009). Unlike TFBSs, however, histone modifications are not necessarily easily localizable to particular sequence elements, making their evolution difficult to study (Delest et al. 2012).Histone 3 lysine 27 trimethylation (H3K27me3) is one of the best-known histone modifications, in terms of both its biogenesis and effects. H3K27me3 is associated with complex cis-regulatory elements called Polycomb Response Elements (PREs) (Delest et al. 2012). Unlike TFBSs, PREs are compound regulatory elements composed of multiple, sometimes partially redundant, sequen...

Cooperativity, Specificity, and Evolutionary Stability of Polycomb Targeting in Drosophila

“…In fact, the evolutionary profile of epigenomic domain organization in embryos of five Drosophila species indicates a complete lack of divergence of H3K27me3-marked Polycomb domains in syntenic regions. A similar high conservation of the H3K27me3 pattern across Drosophila species was recently described (Arthur et al, 2014). Polycomb domains typically harbor several PH-marked PREs, and a comparative analysis showed that these are also highly conserved and the few loci that show a divergence of PRC1 occupancy patterns are not correlated with overall domain divergence.…”

Recent Cis-Trans Coevolution Driven by the Emergence of A Novel Gene in Drosophila

“…Functional analyses suggest that Zeus evolved specific roles in the development and function of Drosophila sperm and testis 2 . This evolution in Zeus' function coincided with changes in its expression and patterns of histone modification at the Zeus locus 11 . In contrast, its parental gene Caf40 (CG14213, also known as Rcd-1), conserved across eukaryotes, is ubiquitously expressed and is essential for viability in Drosophila melanogaster 2 …”

Underrepresentation of active histone modification marks in evolutionarily young genes

“…However, as introduced previously, although epigenetic modifications are also important in regulating gene expression and are well studied in various biological processes, it is rarely explicitly studied in the new gene origination process. Nevertheless, some exciting results are just emerging as demonstrated in a few very recent studies on how epigenetic evolution accompanied transcriptional divergence of duplicated genes (Arthur et al, 2014;Keller & Yi, 2014;Wang et al, 2014). Different from these pioneering works, we directly examined how various histone modifications evolve dynamically across hundreds of million years by classifying genes into more than 10 different age groups (Fig.…”

“…By contrast, although epigenetic mechanisms are also critical to gene expression regulation (Kouzarides, 2007;Li et al, 2007;Brown & Bachtrog, 2014), little is known about their roles in expressional evolution of new genes. It was not until very recently that two important epigenetic mechanisms, that is, DNA methylation and histone modifications, were found to be implicated in the transcriptional divergence of duplicated new genes and their parental copies (Arthur et al, 2014;Keller & Yi, 2014;Wang et al, 2014).…”