アクティブボード・2017年10月
・・・・・2017年10月 1日更新・・・・・
研究発表を行った学会;
2nd Kumamoto IRCMS International Symposium and 17th Kumamoto AIDS Semina
2016年10月31日〜11月2日(熊本、熊本県民交流会館-パレア)
タイトル;Molecular characterization of a new enhancer in HTLV-1 provirus.
発表者;松尾 美沙希 氏
(熊本大学 国際先端医学研究拠点施設 エイズ学研究センター 佐藤プロジェクト研究室)
要旨;
There are sense and anti-sense transcriptions from HTLV-1 provirus. ATL cells are characterized by a monoclonal integration of HTLV-1 provirus in the host genomic DNA. In ATL cells, the sense transcription is frequently silenced, but anti-sense transcription is constitutively active. Recently, we have found that there is a nucleosome free region (NFR) near 3’LTR. The NFR is highly conserved and exhibits enhancer activity. These data indicates that the enhancer region can activate transcription of HBZ from 3'LTR in ATL cells. However, it remains unknown what kind of molecular mechanism is involved in the enhancer activity. In this study, we analyzed histone modifications and transcription factor binding to the enhancer region to elucidate more details about molecular mechanism of the HTLV-1 enhancer region. First, we analyzed several histone modifications in the HTLV-1 provirus by chromatin immunoprecipitation (ChIP)-sequencing technique. Typical histone modifications observed at enhancer regions were found at the NFR, such as H3K27Ac, H3K4me2 and H3K4me3. Second, we predicted the transcription factors binding to the NFR based on the DNA sequence of the NFR. We identified some candidates and analyzed their binding to the NFR by ChIP-seq assay. Then, we found that Serum Response factor (SRF) and Ets-like transcription factor (Elk-1) were bound to the NFR. It has been reported that SRF and Elk-1 form the ternary complex on the consensus DNA binding region and activate transcription. We have analyzed the NFR in the 3'LTR side of the HTLV-1 provirus in more details and identified that SRF and Elk-1 bind to the NFR. We would like to propose that the NFR functions as an enhancer of anti-sense transcription from HTLV-1 provirus.