東京大学 · 生化学・遺伝学・分子生物学
吉田稔教授の研究室は、エピジェネティクス分野に焦点を当て、特にヒストン脱アセチル化酵素(HDAC)の機能解明とその阻害機構の解明を主な研究テーマとしています。Trichostatin A や Trapoxin といった微生物由来のHDAC阻害剤を用いた、染色体構造と遺伝子発現の制御機構の解明が進んでいます。また、これらの阻害剤の作用メカニズムを解明するための新規化合物の合成や、その作用の可逆性・不活性化機構の解明にも取り組んでいます。
Figures are computed from collected data and may differ slightly.
(R)-Trichostatin A (TSA) is a Streptomyces product which causes the induction of Friend cell differentiation and specific inhibition of the cell cycle of normal rat fibroblasts in the G1 and G2 phases at the very low concentrations. We found that TSA caused an accumulation of acetylated histone species in a variety of mammalian cell lines. Pulse-labeling experiments indicated that TSA markedly prolonged the in vivo half-life of the labile acetyl groups on histones in mouse mammary gland tumor ce
The genome of human T-cell leukemia virus (HTLV) was surveyed in fresh tumor cells of 163 patients with lymphoma and leukemia from the southwest part of Japan where adult T-cell leukemia (ATL) is endemic. Leukemic cells of all 88 cases of ATL tested so far were found to contain the provirus genome and also found to be monoclonal with respect to the integration site of provirus genome. In most cases of ATL, leukemic cells contained one or two copies of the complete HTLV provirus genome, and it wa
Reversible acetylation at the epsilon-amino group of lysines located at the conserved domain of core histones is supposed to play an important role in the regulation of chromatin structure and its transcriptional activity. One promising strategy for analyzing the precise function of histone acetylation is to block the activities of acetylating or deacetylating enzymes by specific inhibitors. Recently, two microbial metabolites, trichostatin A and trapoxin, were found to be potent inhibitors of h
Trichostatin A (TSA) and trapoxin (TPX) are potent inhibitors of histone deacetylases (HDACs). TSA is proposed to block the catalytic reaction by chelating a zinc ion in the active-site pocket through its hydroxamic acid group. On the other hand, the epoxyketone is suggested to be the functional group of TPX capable of alkylating the enzyme. We synthesized a novel TPX analogue containing a hydroxamic acid instead of the epoxyketone. The hybrid compound cyclic hydroxamic acid-containing peptide (
X-ray diffraction studies have been made of cubic (3C) and hexagonal (6H) polytypes of SiC under pressures to 105 and 95 GPa, respectively, using a diamond-anvil cell and an imaging plate technique. 3C-SiC undergoes a phase transition into the rocksalt-type structure at 100 GPa or higher accompanied by a volume reduction of 20.3%. The 6H polytype of SiC remains stable to the highest pressure studied, with a premonition of a phase transition above 90 GPa. Equation-of-state data for the two polyty
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