Two large-scale analyses of Ty1 LTR-retrotransposon de novo insertion events indicate that Ty1 targets nucleosomal DNA near the H2A/H2B interface

Abstract

Background: Over the years, a number of reports have revealed that Ty1 integration occurs in a 1-kb window upstream of Pol III-transcribed genes with an approximate 80-bp periodicity between each integration hotspot and that this targeting requires active Pol III transcription at the site of integration. However, the molecular bases of Ty1 targeting are still not understood.

Findings: The publications by Baller et al. and Mularoni et al. in the April issue of Genome Res. report the first high-throughput sequencing analysis of Ty1 de novo insertion events. Their observations converge to the same conclusion, that Ty1 targets a specific surface of the nucleosome at he H2A/H2B interface.

Conclusion: This discovery is important, and should help identifying factor(s) involved in Ty1 targeting. Recent data on transposable elements and retroviruses integration site choice obtained by large-scale analyses indicate that transcription and chromatin structure play an important role in this process. The studies reported in this commentary add a new evidence of the importance of chromatin in integration selectivity that should be of interest for everyone interested in transposable elements integration.

Figure 1

Yeast chromosome with Ty1, 3, 5 integration-targeted regions.

Figure 2

Strategies used to recover insertions: red triangles represent the tag sequences transferred from one LTR to another during retrotransposition. In Baller et al., the tag is a 6 nucleotide substitution, in Mularoni et al., the tag is a 25 bp synthetic DNA.

Figure 3

(A) Plot of Ty1 insertions upstream of tRNAs. The blue curve above the midline represents Ty1 insertions in tandem with the tRNAs, that below the midline represents elements inserted in inverted orientation. (B) Scheme of Ty1 integration in nucleosomal DNA. The black lines represent nucleosomal DNA from base 1 to base 146 (5' to 3' orientation), the red boxes are the hotspots of integration with the coordinates of the attacked dinucleotides indicated above. The green broken lines indicate the expected integration hotspots symmetrically disposed around the dyad axis and distant of 73 bp. We can see here the "right shift" of the observed integration hotspots towards the tRNA gene in regard to the dyad axis of symmetry.