| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Research Abstract |
Functions of eukaryotic chromatin are regulated by various post-translational modification. Methylations of histone lysine residues have distinct functions depending on their positions: H3K27 trimethylation (H3K27me3) marks repressive genes. UTX/KDM6A is an H3K27 specific demethylase involved in animal cell differentiation and cell fate decision.
To elucidate the structural basis for H3K27 specific demethylation by UTX, we determined the crystal structure of its H3 complex, which showed that UTX contains a novel zinc-binding domain in its C-terminus as well as the catalytic Jumonji domain. The jumonji domain accommodates H3 residues around H3K27, whereas the zinc-binding domain recognizes H3L20 and its neighboring residues. Biochemical analysis of mutant UTX showed that these interactions are required for demethylation. Our study
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