Kyoto University

About: Kyoto University is a education organization based out in Kyoto, Japan. It is known for research contribution in the topics: Catalysis & Population. The organization has 85837 authors who have published 217215 publications receiving 6526826 citations. The organization is also known as: Kyōto University & Kyōto daigaku.

Acceleration of intestinal polyposis through prostaglandin receptor EP2 in ApcΔ716 knockout mice

Abstract: Arachidonic acid is metabolized to prostaglandin H(2) (PGH(2)) by cyclooxygenase (COX) COX-2, the inducible COX isozyme, has a key role in intestinal polyposis Among the metabolites of PGH(2), PGE(2) is implicated in tumorigenesis because its level is markedly elevated in tissues of intestinal adenoma and colon cancer Here we show that homozygous deletion of the gene encoding a cell-surface receptor of PGE(2), EP2, causes decreases in number and size of intestinal polyps in Apc(Delta 716) mice (a mouse model for human familial adenomatous polyposis) This effect is similar to that of COX-2 gene disruption We also show that COX-2 expression is boosted by PGE(2) through the EP2 receptor via a positive feedback loop Homozygous gene knockout for other PGE(2) receptors, EP1 or EP3, did not affect intestinal polyp formation in Apc(Delta 716) mice We conclude that EP2 is the major receptor mediating the PGE2 signal generated by COX-2 upregulation in intestinal polyposis, and that increased cellular cAMP stimulates expression of more COX-2 and vascular endothelial growth factor in the polyp stroma

Large histone H3 lysine 9 dimethylated chromatin blocks distinguish differentiated from embryonic stem cells

Abstract: Higher eukaryotes must adapt a totipotent genome to specialized cell types with stable but limited functions. One potential mechanism for lineage restriction is changes in chromatin, and differentiation-related chromatin changes have been observed for individual genes. We have taken a genome-wide view of histone H3 lysine 9 dimethylation (H3K9Me2) and find that differentiated tissues show surprisingly large K9-modified regions (up to 4.9 Mb). These regions are highly conserved between human and mouse and are differentiation specific, covering only approximately 4% of the genome in undifferentiated mouse embryonic stem (ES) cells, compared to 31% in differentiated ES cells, approximately 46% in liver and approximately 10% in brain. These modifications require histone methyltransferase G9a and are inversely related to expression of genes within the regions. We term these regions large organized chromatin K9 modifications (LOCKs). LOCKs are substantially lost in cancer cell lines, and they may provide a cell type-heritable mechanism for phenotypic plasticity in development and disease.