| 研究実績の概要 |
On the basis of the young scientist (B) research project, recently I have reported a role for the SRA protein NP95 to recognize ectopic hemi-methylated DNA, induced by acute depletion of DNMT1, for aberrant activation of specific LTR-derived sequences in the genome (Sharif et al., Cell Stem Cell, 2016). I have previously shown that hemi-methylated DNA recognition by NP95 is essential for maintenance of DNA methylation in mammals (Sharif et al., Nature, 2007). Therefore, in the recent paper I extend this previous finding by showing that the association of NP95 to hemi-methylated DNA could lead to a sequence of epigenetic events, notably, disruption of SETDB1-mediated H3K9me3 pathway that represses LTR-derived sequences. I have also shown that such NP95 and hemi-methylated DNA interactions could play a role to induce robust transcription of LTR-derived sequences in the placenta. LTR-derived sequences were thought to be silenced in most, if not all, cell types; and my research shows that this is not the case. Instead, an interplay between NP95, hemi-methylated DNA and SETDB1 ensures silencing of LTR-derived sequences in the embryo proper, but paradoxically allows the transcription of such parasitic sequences in the extra-embryonic tissues (e.g placenta).
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