组蛋白去乙酰化酶抑制剂对异染色质的影响：对癌症治疗有何启示？
The effects of histone deacetylase inhibitors on heterochromatin: implications for anticancer therapy?
作者信息
Taddei Angela, Roche Danièle, Bickmore Wendy A, Almouzni Geneviève
机构信息
Institut Curie, Research Section, UMR 218 du CNRS, 26 Rue d'Ulm, 75248 Paris cedex 05, France.
出版信息
EMBO Rep. 2005 Jun;6(6):520-4. doi: 10.1038/sj.embor.7400441.
Abstract
Histone acetylation regulates many chromosome functions, such as gene expression and chromosome segregation. Histone deacetylase inhibitors (HDACIs) induce growth arrest, differentiation and apoptosis of cancer cells ex vivo, as well as in vivo in tumour-bearing animal models, and are now undergoing clinical trials as anti-tumour agents. However, little attention has been paid to how HDACIs function in these biological settings and why different cells respond in different ways. Here, we discuss the consequences of inhibiting histone deacetylases in cycling versus non-cycling cells, in light of the dynamics of histone acetylation patterns with a specific emphasis on heterochromatic regions of the genome.
摘要
组蛋白乙酰化调节许多染色体功能，如基因表达和染色体分离。组蛋白去乙酰化酶抑制剂（HDACIs）在体外以及在荷瘤动物模型体内均可诱导癌细胞的生长停滞、分化和凋亡，目前正作为抗肿瘤药物进行临床试验。然而，对于HDACIs在这些生物学环境中的作用方式以及不同细胞为何有不同反应，人们关注较少。在此，我们根据组蛋白乙酰化模式的动态变化，特别是着重于基因组的异染色质区域，来讨论在循环细胞与非循环细胞中抑制组蛋白去乙酰化酶的后果。
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