Trans-inactivation: Repression in a wrong place

Funikov

Protsenko

et al. 2021

Genes

Pericentromeric heterochromatin in Drosophila generally consists of repetitive DNA, forming the environment associated with gene silencing. Despite the expanding knowledge of the impact of transposable elements (TEs) on the host genome, little is known about the evolution of pericentromeric heterochromatin, its structural composition, and age. During the evolution of the Drosophilidae, hundreds of genes have become embedded within pericentromeric regions yet retained activity. We investigated a pericentromeric heterochromatin fragment found in D. virilis and related species, describing the evolution of genes in this region and the age of TE invasion. Regardless of the heterochromatic environment, the amino acid composition of the genes is under purifying selection. However, the selective pressure affects parts of genes in varying degrees, resulting in expansion of gene introns due to TEs invasion. According to the divergence of TEs, the pericentromeric heterochromatin of the species of virilis group began to form more than 20 million years ago by invasions of retroelements, miniature inverted repeat transposable elements (MITEs), and Helitrons. Importantly, invasions into the heterochromatin continue to occur by TEs that fall under the scope of piRNA silencing. Thus, the pericentromeric heterochromatin, in spite of its ability to induce silencing, has the means for being dynamic, incorporating the regions of active transcription.

Section: Resultsmentioning

confidence: 99%

Evolutionary Dynamics of the Pericentromeric Heterochromatin in Drosophila virilis and Related Species

Funikov

Protsenko

et al. 2021

Genes

“…A distinctive feature of heterochromatin is the ability to silence euchromatic genes placed within heterochromatic environment due to chromosomal inversions or transposition events, a phenomenon called position effect variegation (PEV) 7 – 12 . It is generally believed that transcriptional silencing of euchromatic genes in PEV is mediated by spreading of heterochromatin-associated marks HP1a and H3K9me3 across the gene loci transferred to heterochromatin 8 , 10 .…”

Section: Introductionmentioning

confidence: 99%

Adaptation of gene loci to heterochromatin in the course of Drosophila evolution is associated with insulator proteins

Funikov

Куликова

et al. 2020

Sci Rep

Pericentromeric heterochromatin is generally composed of repetitive DNA forming a transcriptionally repressive environment. Dozens of genes were embedded into pericentromeric heterochromatin during evolution of Drosophilidae lineage while retaining activity. However, factors that contribute to insusceptibility of gene loci to transcriptional silencing remain unknown. Here, we find that the promoter region of genes that can be embedded in both euchromatin and heterochromatin exhibits a conserved structure throughout the Drosophila phylogeny and carries motifs for binding of certain chromatin remodeling factors, including insulator proteins. Using ChIP-seq data, we demonstrate that evolutionary gene relocation between euchromatin and pericentric heterochromatin occurred with preservation of sites of insulation of BEAF-32 in evolutionarily distant species, i.e. D. melanogaster and D. virilis . Moreover, promoters of virtually all protein-coding genes located in heterochromatin in D. melanogaster are enriched with insulator proteins BEAF-32, GAF and dCTCF. Applying RNA-seq of a BEAF-32 mutant, we show that the impairment of BEAF-32 function has a complex effect on gene expression in D. melanogaster, affecting even those genes that lack BEAF-32 association in their promoters. We propose that conserved intrinsic properties of genes, such as sites of insulation near the promoter regions, may contribute to adaptation of genes to the heterochromatic environment and, hence, facilitate the evolutionary relocation of genes loci between euchromatin and heterochromatin.

“…A distinctive feature of heterochromatin is the ability to silence euchromatic genes placed within heterochromatic environment due to chromosomal inversions or transposition events, a phenomenon called position effect variegation (PEV) (7-12). Transcriptional silencing of euchromatic genes in PEV is mediated by spreading of heterochromatin-associated marks HP1a and H3K9me3 across the gene loci transferred to heterochromatin (8,10).…”

Section: Introductionmentioning

confidence: 99%

Insulator proteins contribute to expression of gene loci repositioned into heterochromatin in the course ofDrosophilaevolution

et al. 2019

Preprint

1 2 3 4 5 7 8of Drosophila melanogaster. Interestingly, genes embedded in pericentric heterochromatin of D. melanogaster may occupy different genomic loci, euchromatic or heterochromatic, due to repositioning in the course of evolution of Drosophila species. By surveying factors that contribute to the normal functioning of the relocated genes in distant Drosophila species, i.e. D. melanogaster and D. virilis, we identify certain insulator proteins (e.g.BEAF-32) that facilitate the expression of heterochromatic genes in spite of the repressive environment.Despite the repressive environment, dozens of essential genes were identified in the pericentric heterochromatin of D. melanogaster (13)(14)(15)(16). Interestingly, genes embedded in pericentric heterochromatin in D. melanogaster may occupy distinct genomic loci, euchromatic and heterochromatic, in other Drosophila species (17). For instance, two adjacent genes RpL15 and Dbp80 located in the pericentric region of chromosome 3L in D. melanogaster reside in a euchromatic region in D. pseudoobscura (18). A similar pattern was demonstrated for genes light and Yeti located in pericentric regions in D. melanogaster, while in D. virilis they are found within euchromatin on the same chromosomal elements (19,20). Recently, it was shown that most of the pericentric genes found at both arms of chromosome 2 of D. melanogaster are located in euchromatic loci in the D. virilis genome (21). However, although repositioning of genes between euchromatin and heterochromatin during genome evolution is not unusual in the Drosophilidae lineage, the "immunity" of heterochromatic genes to the transcriptionally repressive environment remains paradoxical and unexplained. Thus, it is not clear whether these loci have undergone adaptation to heterochromatic environment or had some intrinsic properties permitting local adaptation.Previously, it was shown that molecular organization of promoter regions is largely conserved between heterochromatic and euchromatic genes, indicating that adaptation to heterochromatin probably does not require major changes in regulatory sequences (20). However, expression of heterochromatic genes requires the methylated H3K9 mark (22,23), and the ability to repositioning during evolution is a characteristic feature of gene clusters that show close association with HP1a protein (21).Chromatin insulator elements and associated proteins were originally defined by their ability to protect transgenes from PEV, exerting a block to cis spreading of a chromatin state (24, 25). To date, a set of insulators have been identified in Drosophila, including BEAF-32 (Boundary element associated factor of 32 kDa), dCTCF (Drosophila homolog of CTCF), Su(Hw) (Suppressor of hairy wing), Zw5 (Zeste-white-5), GAF (GAGA factor) and recently expression of heterochromatic genes and make them predisposed for evolutionary repositioning into transcriptionally repressive genomic environments. Results Evolutionary repositioning of Myb and Ranbp16 genes between euchromatin and heterochromatin...