CHD4在染色体重塑中的作用

染色质作为真核细胞遗传信息,体内外各种因素的作用致使不断的产生损伤,但是细胞仍能保持正常的生长、分裂和繁殖,这与基因组稳定性和完整性保持,并且通过自身的损伤修复有着密切的联系。ATP依赖的染色质重塑是染色质重塑的最重要的方式之一,主要是利用ATP水解释放的能量,将凝聚的异染色质打开,协调损伤修复蛋白与DNA损伤位点的作用,通过对组蛋白的共价键修饰或ATP依赖的染色质重塑复合物开启了DNA的损伤修复的大门。CHD4/Mi-2β的类SWI2/SNF2 ATP酶/解螺旋酶域结构域保守性最强,这一结构域存在与多种依赖于ATP的核小体重构复合物。Mi-2蛋白复合物称为核小体重塑及去乙酰化酶NuRd(nucleoside remodeling and deacetylase,NuRD),是个多亚基蛋白复合物,Mi2β/CHD4是该复合物的核心成员。近来的研究发现,CHD4具有染色质重塑功能,并且参与DNA损伤修复的调控。CHD4羧基端的PHD通过乙酰化或甲基化识别组蛋白H3氨基端Lys9(H3K9ac和H3K9me),并且通过Lys4甲基化(H3K4me)或Ala1乙酰化(H3A Lac)抑制与H3、H4的结合,为染色质重塑提供了保障。Mi-2β/CHD4参与DNA损伤反应,定位于DNA损伤γ-H2AX的foci。沉默Mi-2β/CHD4基因,细胞自发性DNA损伤增多和辐射敏感性增强。表明CHD4在染色质重塑中具有重要的作用。

Effect of CHD4 in Chromatin Remodeling

It is necessary for the conservation and genomic stability and integrity of chromatin to prevent from various factors causing continuous damage and keep cell maintain normal growth, division and reproduction in vitro and vivo. ATP- Dependent Chromatin-Remodeling that is one of the most important way of DNA damage repair response mainly exposure chromatin condensation by the energy of ATP hydrolysis and coordinate effect of the damage repair protein and the sites of DNA damage by histone covalent modifications or ATP- Dependent Chromatin-Remodeling Complexes which open the door of DNA damage repair response.It is recently reported that CHD4 can participate in the regulation of DNA damage repair with functions of chromatin remodeling. It is very important that the second PHD finger （PHD2） of CHD4 recognizes the N-terminus of histone H3 and that this interaction is facilitated by acetylation ormethylation of Lysg（H3K9ac andH3Kgme respectively） but is inhibited by methylation of Lys4（H3K4me） or acetylation of Alal （H3Alac） to provide protection for chromatin remodeling. Mi-213 / CHD4 is Colocalization with ~-H2AX foci in the DNA damage response. Silence Mi - 2 beta/CHD4 genes, cells increase spontaneous DNA damage and radiation sensitivity. Show CHD4 in chromatin remodeling plays an important role.Silence Mi-213/CHD4 regulates cell sensitivity to spontaneous DNA damage and radiosensitivity. CHD4 has an important role in chromatin remodeling.