アクティブボード・２００９年　９月
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研究発表を行った学会；
・International Joint Symposium on "Cell Fate Regulation Research:
Molecular Basis and Therapeutic Potentials".
　２００９年４月９日〜１０日（熊本）

タイトル；Architectural roles of multiple chromatin insulators at the human apolipoprotein gene cluster.
　
発表者；　三代　剛　氏
　　　（熊本大学　発生医学研究所　細胞医学分野）

Abstract；
Long-range regulatory elements and higher-order chromatin structure coordinate the expression of multiple genes in cluster, and CTCF/cohesin-mediated chromatin insulator may be a key in this regulation. The human apolipoprotein (APO) A1/C3/A4/A5 gene region, whose alterations increase the risk of dyslipidemia and atherosclerosis, is partitioned at least by three CTCF-enriched sites and three cohesin protein RAD21-enriched sites (two overlap with the CTCF sites), resulting in the formation of two transcribed chromatin loops by interactions between insulators. The C3 enhancer and APOC3/A4/A5 promoters reside in the same loop, where the APOC3/A4 promoters are pointed towards the C3 enhancer, whereas the APOA1 promoter is present in the different loop. The depletion of either CTCF or RAD21 disrupts the chromatin loop structure, together with significant changes in the APO expression and the localization of transcription factor hepatocyte nuclear factor (HNF)-4a and transcriptionally active form of RNA polymerase II at the APO promoters. Thus, CTCF/ cohesin-mediated insulators maintain the chromatin loop formation and the localization of transcriptional apparatus at the promoters, suggesting an essential role of chromatin insulation in controlling the expression of clustered genes.

The EMBO Journal (2009) 28, 1234–1245.