アクティブボード・２０１６年１２月
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研究発表を行った学会；
・2nd Kumamoto IRCMS International Symposium and 17th Kumamoto AIDS Seminar
　　2016年10月31日〜11月2日（熊本）

タイトル；SOX2 is a key factor for the expression of HERV-K LTR5-Hs.
発表者；門出　和精　氏
　　　（熊本大学　大学院生命科学研究部　微生物学分野）
要旨；
Human endogenous retroviruses (HERVs) comprise approximately 8% of human genome. HERVs are constitutively transcribed in primordial germ cells. Eventually, transcription of HERV-K is silenced except for in pathological contexts such as teratocarcinoma. It has been reported that HERV-K would be required for protecting the embryo from exogenous viral infection. On the other hand, uncontrollable HERV-K expression is speculated to contribute the pathogenesis of cancer and AIDS. To determine the causal relationship between HERV-K expression and these diseases, it is necessary to reveal the regulatory mechanism of HERV-K transcription. In this study, we found that transcription of HERV-K was activated in Sox2-transfected HeLa cells. Expression of endogenous HERV-K Gag mRNA in HeLa cells was increased by overexpression of both Sox2 and Klf4. Furthermore, we were able to detect the Sox2-binding HERV-K DNA with an anti-Sox2 antibody using ChIP assay in teratocarcinoma cells. Interestingly, fifteen Sox2-binding regions were encoded and conserved among HERV-K LTR5Hs that is known to represent most recent germline-integrated HERV-K family. The multiple deletions of Sox2-binding regions in HERV-KCON LTR lost the transcription activity. Altogether, these results indicate that Sox2 is a key transcriptional factor for HERV-K expression. Indeed, we consistently found the expression of HERV-K Gag mRNA in human iPS cells. Our data suggest that HERV-K is likely to be expressed in short-term period of early development to play a role for development of embryo. In contrast, it is also concerned that long-term culturing upon overexpression of Sox2 might trigger HERV-K retrotransposition in human iPS cells.