Abstract

BackgroundThe long terminal repeat (LTR) retrotransposons and the non-LTR retrotransposons (LINE-1 or L1) make up more than one-third of the mouse genome. Because of their abundance, the retrotransposons are the major players in genomic structure and function. While much attention has been focused on the biology of retrotransposons, little is known about the chromatin structure of these elements or the potential role of epigenetic marks on the regulation of retrotransposon expression.FindingsUsing sequential chromatin immunoprecipitation analysis, we analyzed the cohabitation of several post-translational histone modifications in the promoter regions of mouse L1 and LTR retrotransposons. We show here that the variant histone H2A.Z selectively present in L1 promoters. Notably, H2A.Z and trimethylated histone H3 (H3K9me3) co-localize in the same genomic location of the L1 promoter along with heterochromatin-binding protein HP1α. In contrast, MmERV and intracisternal A-particle (IAP) classes of LTR promoters are enriched with core histone H2A and heterochromatic trimethylated histone H4 (H4K20me3). These distinctive patterns of chromatin modifications are relatively consistent irrespective of cell type.ConclusionsChromatin structure regulates the expression of retrotransposons. LINE-1 elements are associated with H2A.Z and HP1α-containing constitutive heterochromatin, while the LTR elements are enriched with H2A and the H4K20me3-type of facultative heterochromatin. Our findings demonstrate that different epigenetic mechanisms operate in the mouse genome to silence different classes of retrotransposons.

Highlights

  • The long terminal repeat (LTR) retrotransposons and the non-LTR retrotransposons (LINE-1 or L1) make up more than one-third of the mouse genome

  • Long interspersed nuclear element-1 (LINE-1) elements are associated with H2A.Z and HP1α-containing constitutive heterochromatin, while the LTR elements are enriched with H2A and the H4K20me3-type of facultative heterochromatin

  • Genomic DNA associated with H2A, and H2A.Z chromatin-bound fragments was purified, and using consensus primers to detect multiple copies of L1, SINE-B1, and LTR (MmERV and intracisternal A-particle (IAP))-elements, we subjected it to qPCR analysis to determine the relative abundance of H2A and H2A.Z in different retrotransposons (Figure 1A)

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Summary

Conclusions

Chromatin structure regulates the expression of retrotransposons. LINE-1 elements are associated with H2A.Z and HP1α-containing constitutive heterochromatin, while the LTR elements are enriched with H2A and the H4K20me3-type of facultative heterochromatin.

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Kouzarides T
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