アクティブボード・２０１３年　７月
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研究発表を行った学会； The 2nd JSGE International Topic Conference
・２０１３年３月２３日（鹿児島）

タイトル；The regulation of Lymphotoxinβ is involved in the higher- order chromatin conformation of the TNF/LT locus in hepatocellular carcinoma cells.
発表者；渡邊　丈久　氏
　　　（熊本大学　大学院生命科学研究部　消化器内科学分野）
Abstract；
The tumor necrosis factor (TNF) superfamily members, TNF (initially termed TNF-α), lymphotoxin-α (LTα), and lymphotoxin-β (LTβ), are major pro-inflammatory cytokines that mediate inflammatory responses. In addition to their physiological roles, the aberrant or unbalanced expression of these cytokines is linked to pathological conditions, including cancer development. Especially, LTβ expression is significantly involved in liver inflammation, regeneration and hepatocellular carcinomas (HCCs). The TNF/LT genes are sequentially located and differently regulated. However, the regulatory mechanisms have been poorly understood.
We have demonstrated a transcriptional mechanism and higher-order chromatin regulation in the TNF/LT locus with chromosome conformation capture (3C) analyses. In this context, we identified at least four CTCF/cohesin-enriched insulators and a TNF responsive TE2 enhancer in human hepatic cells. The interactions between TE2 enhancer and LTβ promoter, which activate LTβ gene transcription, were found to be regulated by insulator-mediated chromatin conformation. In addition, the results of the following immune-histochemical analyses of human HCC tissues to examine LTβ expression in vivo may support our finding. In conclusion, to investigate the relationship between LTβ expression and chromosomal conformation of the TNF/LT locus may provide a novel therapeutic strategy for chronic hepatitis as well as HCC.