曲古抑菌素A
组蛋白脱乙酰基酶
组蛋白脱乙酰基酶2
HDAC1型
染色质免疫沉淀
组蛋白脱乙酰基酶5
HDAC11型
化学
组蛋白
染色质
丁酸盐
抄写(语言学)
细胞生物学
癌症研究
生物化学
生物
基因表达
发起人
DNA
基因
发酵
语言学
哲学
作者
Anoushe Sekhavat,Jianmin Sun,James Davie
摘要
Histone deacetylases (HDACs) play a pivotal role in gene expression through their involvement in chromatin remodeling. The abnormal targeting or retention of HDACs to DNA regulatory regions is observed in many cancers, and hence HDAC inhibitors are being tested as promising anti-tumor agents. The results of previous kinetic studies, characterizing trichostatin A (TSA), as well as butyrate, as HDAC noncompetitive inhibitors, conflict with crystallographic and homology modeling data suggesting that TSA should act as a competitive inhibitor. Our results demonstrate that each of the HDAC inhibitors TSA and butyrate inhibits HDAC activity in a competitive fashion. Co-immunoprecipitation studies show that the inhibition of HDAC1 and HDAC2 activity by TSA does not disturb the extensive level of their association in the human breast cancer cell line MCF-7. Moreover, the inhibition of HDAC activity by TSA does not interfere with the interaction of HDAC1 and HDAC2 with Sin3A, a core component of the Sin3 complex. Thus, repressor complexes such as Sin3, appear to be stable in the presence of TSA. The association of HDAC2 with transcription factor Sp1 is also not affected by TSA.
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