Transcriptional regulation of human-specific SVAF1 retrotransposons by cis-regulatory MAST2 sequences

SVA elements represent the youngest family of hominid non-LTR retrotransposons. Recently, a human-specific subfamily (termed SVAF1, CpG-SVA, or MAST2-SVA) was discovered representing fusion of the CpG island-containing exon 1 of the MAST2 gene and a 5′-truncated SVA. SVAF1 includes at least 84 members, which suggests exceptionally high retrotransposition level. We investigated if the acquirement of the MAST2 CpG-island might play a role in the success of the SVAF1 subfamily. We observed that in 16 samples representing seven human tissues, MAST2 was cotranscribed with the members of the SVAF1 subfamily, but not with other retrotransposons. We found that the methylation status of the MAST2-derived sequences of SVAF1 elements reversely correlates with the transcriptional activity of MAST2. The MAST2 sequence at the 5′ end of SVAF1 acts as a positive transcriptional regulator in human germ cells. Finally, in various testicular tissue samples we uncovered a transcriptional correlation of MAST2 with the human L1, Alu and SVA retrotransposons.

► SVAF1 (CpG-SVA) family consists of at least 84 human specific hybrid retrotransposons.
► 5′ terminal sequence of SVAF1 evolved from the exon 1 of the gene MAST2.
► We show that SVAF1 and MAST2 display similar transcriptional pattern in human tissues.
► MAST2–derived sequence acts as positive transcriptional regulator of SVAF1 elements.
► MAST2 is cotranscribed with many mammalian retrotransposons in testicular tissue.