Grant-in-Aid for Scientific Research (B)
Chronic inflammation of endothelial cell is the first stage ofatherogenesis. We applied an experimental model using endothelial cells with representative inflammatory stimulant, tumor necrosis factor-alpha (TNFα), and to dissect detailedmechanism of induction and reduction of more than 500 genes. To obtain a comprehensive view of a single transcription cycle caused by TNFα in time course manner, we switched onfive long (>100 kbp) genes with TNFα and monitored genomic localization of nascent RNA, RNA Pol II, insulators, and histone modifications. Activation triggers a wave of transcriptionthat sweeps along the genes, and Pol II tends to stall at cohesin/CTCF binding sites. Chromatin conformation capture (3C), both conventional and quantitative data, revealedco-localization of actively transcribed genes. These results suggested that fine-tuning of TNFα responsive genes is achieved by selected number of transcription complexes, whichprovide platform for both transcription and splic ng. By virtue of whole genome chromatininteraction analysis with paired end tag sequencing (ChIA-PET) detailed chromatin structureanalysis was made possible, and time course data on stimulated endothelium sheds light ondynamic chromatin structure change within half an hour.
Mol Cell Biol
J Clin Invest.
Phys Rev E Stat Nonlin Soft Matter Phys
Volume: (In press)
Journal of pharmacological sciences
Proceedings of the National Academy of Science
Nucleic Acids Research
The Journal of Biological Chemistry
Molecular and Cellular Biology
Journal of Pharmacological Sciences
The EMBO Journal
Volume: (in press(掲載確定),in press(掲載確定))
mobile or immobile molecular machines PLoS biology 8
Attribution of KAKENHI