Chromodomains direct integration of retrotransposons to heterochromatin

Abstract

The enrichment of mobile genetic elements in heterochromatin may be due, in part, to targeted integration. The chromoviruses are Ty3/gypsy retrotransposons with chromodomains at their integrase C termini. Chromodomains are logical determinants for targeting to heterochromatin, because the chromodomain of heterochromatin protein 1 (HP1) typically recognizes histone H3 K9 methylation, an epigenetic mark characteristic of heterochromatin. We describe three groups of chromoviruses based on amino acid sequence relationships of their integrase C termini. Genome sequence analysis indicates that representative chromoviruses from each group are enriched in gene-poor regions of the genome relative to other retrotransposons, and when fused to fluorescent marker proteins, the chromodomains target proteins to specific subnuclear foci coincident with heterochromatin. The chromodomain of the fungal element, MAGGY, interacts with histone H3 dimethyl-and trimethyl-K9, and when the MAGGY chromodomain is fused to integrase of the Schizosaccharomyces pombe Tf1 retrotransposon, new Tf1 insertions are directed to sites of H3 K9 methylation. Repetitive sequences such as transposable elements trigger the RNAi pathway resulting in their epigenetic modification. Our results suggest a dynamic interplay between retrotransposons and heterochromatin, wherein mobile elements recognize heterochromatin at the time of integration and then perpetuate the heterochromatic mark by triggering epigenetic modification.[Supplemental material is available online at www.genome.org.] (Girard et al. 2006;Grivna et al. 2006;Vagin et al. 2006). Mobile element insertions that decorate eukaryotic genomes, therefore, frequently define unique chromatin domains. Whereas the genetic consequences of transposition in terms of mutation and genome rearrangement have long been recognized, the biological consequences of their epigenetic marks, which include effects on gene expression and the formation of heterochromatin, are only beginning to be appreciated (Slotkin and Martienssen 2007).Underlying the genetic and epigenetic impact of mobile elements is integration site choice. Although forces such as selection or recombination contribute to the nonrandom distribution of mobile elements in eukaryotic genomes, an increasing number of studies indicate that many mobile elements target integration to specific chromosomal sites (Bushman 2003). For some elements, target sites are determined by recognizing specific DNA sequences, whereas for others, including several retrotransposons and retroviruses, chromatin impacts target site choice. The Ty1 and Ty3 retrotransposons of Saccharomyces cerevisiae, for example, integrate near sites of RNA polymerase III (pol III) transcription by recognizing pol III transcription complexes or chromatin states associated with pol III transcription (Yieh et al. 2000(Yieh et al. , 2002Bachman et al. 2005;Mou et al. 2006). The Tf1 retrotransposon of Schizosaccharomyces pombe recognizes certain RNA polymerase II (pol II) promoters (Singleton and L...

Long-read sequencing uncovers the adaptive topography of a carnivorous plant genome

“…1A, most U. gibba CRMs are located in the putative centromeric regions; however, not all putative centromeres have CRM elements. It has been proposed that CRMs may play an important role in stabilizing centromere structure and maintaining centromere function (26,27), whereas an opposing hypothesis holds that they are merely parasitic and tend to accumulate in recombination-poor centromeric regions to escape negative selection against insertions in distal regions (28). Our finding that some putative centromeric regions in U. gibba lack CRMs or other high-copy centromeric tandem repeats suggests that neither CRMs nor tandem repeats are crucial for maintaining functional centromeres in the species.…”

Genome sequence of the hot pepper provides insights into the evolution of pungency in Capsicum species

“…18 and 19). Del elements are known to selectively accumulate in heterochromatic regions owing to the function of the encoded chromodomain 24 . However, we often found these Del elements in the collinear regions of the hot pepper genome that correlated with tomato euchromatin, with the insertion of these elements resulting in the formation of heterochromatic gene islands in the hot pepper genome (Fig.…”

Insulator and Ovo Proteins Determine the Frequency and Specificity of Insertion of the gypsy Retrotransposon in Drosophila melanogaster

“…Evidence demonstrating tethering of integrases as a mechanism capable of targeting retroviruses to specific DNA binding sites has been shown in experiments using fusion proteins in which the DNA binding domain of phage l-repressor was fused to the integrase of the HIV retrovirus and successfully showed preferential integra-tion into target DNA near l-repressor-binding sites (Bushman 1994). Similarly, experiments with yeast retrotransposons have shown that such interactions may occur between the retrotransposon integrase and proteins that target the integration to their cognate chromosomal DNA binding sites (Gai and Voytas 1998;Xie et al 2001;Sandmeyer 2003;Zhu et al 2003;Gao et al 2008).…”

“…The best examples of site-specific integration are found in non-LTR retrotransposons such as the Drosophila telomeric elements HeT-A, TART, and TAHRE or rDNA elements such as the Drosophila R1 and R2 non-LTR retrotransposons (Yang et al 1999;Christensen and Eickbush 2005;George et al 2006). A number of examples involving integrases from yeast LTR retrotransposons have also shown that retroviral-like integrases have evolved to acquire strong site-specific integration properties (Sandmeyer 2003;Zhu et al 2003;Brady et al 2008;Gao et al 2008). For example, the integration of Saccharomyces cerevisiae retrotransposons Ty1 and Ty3 is associated with RNA polymerase III transcription (Yieh et al 2000;Bachman et al 2005;Mou et al 2006) and the Tf1 retrotransposon from Schizosaccharomyces pombe integrates near RNA polymerase II promoters (Singleton and Levin 2002;Bowen et al 2003).…”

“…Targeting of the Ty5 retrotransposon from S. cerevisiae to heterochromatin, for example, requires a six-amino-acid motif at the C terminus of the Ty5 integrase that interacts with the heterochromatin protein Sir4 (Gai and Voytas 1 1998;Xie et al 2001). It has also been proposed that the chromodomain (CHD domain) from certain transposable element chromointegrases targets the retrotransposon for insertion into sites bearing the specific epigenetic marks recognized by the CHD domain (Gao et al 2008).…”