组蛋白去乙酰化酶抑制剂(HDAIs)对异染色质的作用

组蛋白乙酰化和去乙酰化可调节染色体的多种功能,例如基因表达和染色体分离等。研究发现,组蛋白去乙酰化酶抑制剂(histone deacetylase inhibitors,HDACIs)可诱导分化、生长阻断和肿瘤细胞凋亡,目前HDACIs正作为抗肿瘤药物进行临床试验,在肿瘤治疗中显示出具有较好的应用前景。然而,人们对于HDACIs在生物体内是如何发挥作用以及不同类型细胞为何会有不同的应答途径却关注甚少。本综述通过讨论HDACIs对周期和非周期细胞中组蛋白去乙酰化酶的抑制结果,来阐明组蛋白乙酰化模式的动力学特征,特别是对基因组异染色质的作用。

The effects of histone deacetylase inhibitors on heterochromatin

Histone acetylation and deacetylation can regulate many chromosome functions,such as gene expression and chromosome segregation.Histone deacetylase inhibitors(HDACIs)induce growth arrest,differ-entiation and apoptosis of cancer cells,and are now undergoing clinical trials as anti-tumor agents and display attractive prospect in cancer therapy.However,little attention has been paid to how HDACIs function in these biological settings and why different cells respond in different ways.In this review,we discussed 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.