组蛋白去乙酰化酶SIR2与染色质沉默

DNA的大部分区域通过包装成特殊的染色质结构而失去活性称为染色质沉默。这些特殊的染色质结构在维持染色体结构稳定和基因调控中起重要作用。有实验表明，沉默染色质的组蛋白H3和H4的的氨基末端尾部相对于基因组的其他区域是低乙酰化的。组蛋白去乙酰化酶SIR2（silent information regulator2）是参与染色质沉默的一种重要的蛋白质。SIR2具有两种相关联的酶活性，组蛋白去乙酰化酶活性和NAD高能骨架的断裂活性，并在酶反应过程中产生一种新的产物氧代乙酰基ADP核糖基（O-acetyl-ADP-ribose）。SIR2的组蛋白去乙酰化酶活性为研究SIR2与沉默染色质的组蛋白低乙酰化状态的关系提供了直接证据。而SIR2的这两种酶活性的关系也表明，组蛋白去乙酰化酶活性不是SIR2惟一的功能。SIR2的NAD水解酶活性和O-acetyl-ADP-ribose的合成过程也可能是染色质沉默机制所必需的。Abstract:Chromatin silencing is the inactivation of large domains of DNA by packaging them into a specialized inaccessible chromatin structure.This type of inactivation is involved in the regulation of gene expression and is also associated with the chromosome structures required for chromosome maintenance and inheritance.Silent information protein 2(SIR2) is one of the important proteins involved in chromatin silencing.It is clear that SIR2 has two coupled enzymatic activities,histone deacetylation and NAD breakdown activities,and produces a novel compound,O-acetyl-ADP-ribose in the enzymatic reactions.The histone deacetylation activity of SIR2 provides the direct link between SIR2 and the hypoacetylation of silent chromatin.Moreover,the relationship between the NAD cleavage and the deacetylase activity of SIR2 shows that the histone deacetylase activity is not its only crucial function.The breakdown of NAD C-N bond and the synthesis of O-acetyl-ADP-ribose may also be involved in chromatin silencing.

The Histone Deacetylase Activity of SIR2 and Chromatin Silencing

Chromatin silencing is the inactivation of large domains of DNA by packaging them into a specialized inaccessible chromatin structure. This type of inactivation is involved in the regulation of gene expression and is also associated with the chromosome structures required for chromosome maintenance and inheritance. Silent information protein 2(SIR2) is one of the important proteins involved in chromatin silencing. It is clear that SIR2 has two coupled enzymatic activities,histone deacetylation and NAD breakdown activities,and produces a novel compound,O-acetyl-ADP-ribose in the enzymatic reactions. The histone deacetylation activity of SIR2 provides the direct link between SIR2 and the hypoacetylation of silent chromatin. Moreover, the relationship between the NAD cleavage and the deacetylase activity of SIR2 shows that the histone deacetylase activity is not its only crucial function. The breakdown of NAD C-N bond and the synthesis of O-acetyl-ADP-ribose may also be involved in chromatin silencing.