Condensin II Subunit dCAP-D3 Restricts Retrotransposon Mobilization in Drosophila Somatic Cells

Abstract

Retrotransposon sequences are positioned throughout the genome of almost every eukaryote that has been sequenced. As mobilization of these elements can have detrimental effects on the transcriptional regulation and stability of an organism's genome, most organisms have evolved mechanisms to repress their movement. Here, we identify a novel role for the Drosophila melanogaster Condensin II subunit, dCAP-D3 in preventing the mobilization of retrotransposons located in somatic cell euchromatin. dCAP-D3 regulates transcription of euchromatic gene clusters which contain or are proximal to retrotransposon sequence. ChIP experiments demonstrate that dCAP-D3 binds to these loci and is important for maintaining a repressed chromatin structure within the boundaries of the retrotransposon and for repressing retrotransposon transcription. We show that dCAP-D3 prevents accumulation of double stranded DNA breaks within retrotransposon sequence, and decreased dCAP-D3 levels leads to a precise loss of retrotransposon sequence at some dCAP-D3 regulated gene clusters and a gain of sequence elsewhere in the genome. Homologous chromosomes exhibit high levels of pairing in Drosophila somatic cells, and our FISH analyses demonstrate that retrotransposon-containing euchromatic loci are regions which are actually less paired than euchromatic regions devoid of retrotransposon sequences. Decreased dCAP-D3 expression increases pairing of homologous retrotransposon-containing loci in tissue culture cells. We propose that the combined effects of dCAP-D3 deficiency on double strand break levels, chromatin structure, transcription and pairing at retrotransposon-containing loci may lead to 1) higher levels of homologous recombination between repeats flanking retrotransposons in dCAP-D3 deficient cells and 2) increased retrotransposition. These findings identify a novel role for the anti-pairing activities of dCAP-D3/Condensin II and uncover a new way in which dCAP-D3/Condensin II influences local chromatin structure to help maintain genome stability.

Condensin controls mitotic chromosome stiffness and stability without forming a structurally contiguous scaffold

“…Alternately condensin may be overloaded in response to chromosomal damage that occurs in a prolonged metaphase, e.g. , dsDNA breaks (Orth et al, 2012), since condensin has been implicated in prevention of accumulation of DNA damage (Sakamoto et al, 2011, Schuster et al, 2013). We do note that it is possible that there is some condensin I loss during isolation of metaphase chromosomes, given its dynamic binding during mitosis (Gerlich et al, 2006).…”

Recurrent losses and rapid evolution of the condensin II complex in insectsg

“…In Drosophila, chromosome decondensation is often observed in the germlines of sterile interspecies hybrid males and males carrying naturally occurring segregation distorters, raising the possibility that the condensin II complex has evolved under pressure from segregation distorters. Third, the condensin II complex has been shown to localize to retrotransposon sequences and mediate their repression in flies (40) and humans (41). As genomes continually evolve to suppress retrotransposon sequences, intragenomic conflicts involving transposable elements may also drive positive selection in Cap-D3, and potentially the rest of the condensin II complex.…”

Unique features of mutations revealed by sequentially reprogrammed induced pluripotent stem cells

“…Although this experimental phenomenon is interesting, the exact explanation for why such a phenomenon occurred requires more subsequent experimentation. Previous study provided a recurrent deletion mechanism of LTR transposable elements in Drosophila due to double-strand breaks beside the retrotransposon sequence with an opening of the chromatin 58 . However, the underlying molecular mechanism of repeated LINE/LTR deletion occurring in pluripotent stem cells necessitates a more thorough investigation in the future.…”