J Biol Chem. 2014 Jul 25;289(30):20717-26. doi: 10.1074/jbc.M114.568568.
Although mutations or deletions of chromodomain helicase DNA-binding protein 5 (CHD5) have been linked to cancer and implicate CHD5 in tumor suppression, the ATP-dependent activity of CHD5 is currently unknown. In this study, we discovered that CHD5 is a chromatin remodeling factor with a unique enzymatic activity. CHD5 can expose nucleosomal DNA at one or two discrete positions in the nucleosome. The exposure of the nucleosomal DNA by CHD5 is dependent on ATP hydrolysis, but continued ATP hydrolysis is not required to maintain the nucleosomes in their remodeled state. The activity of CHD5 is distinct from other related chromatin remodeling ATPases, such as ACF and BRG1, and does not lead to complete disruption or destabilization of the nucleosome. Rather, CHD5 likely initiates remodeling in a manner similar to that of other remodeling factors but does not significantly reposition the nucleosome. While the related factor CHD4 shows strong ATPase activity, it does not unwrap nucleosomes as efficiently as CHD5. Our findings add to the growing evidence that chromatin remodeling ATPases have diverse roles in modulating chromatin structure.
虽然染色质螺旋酶 DNA 结合蛋白 5（CHD5）的突变或缺失与癌症有关，并暗示 CHD5 参与肿瘤抑制，但 CHD5 的 ATP 依赖性活性目前尚不清楚。在这项研究中，我们发现 CHD5 是一种具有独特酶活性的染色质重塑因子。CHD5 可以在核小体的一个或两个离散位置暴露核小体 DNA。CHD5 对核小体 DNA 的暴露依赖于 ATP 水解，但不需要继续 ATP 水解来维持重塑状态的核小体。CHD5 的活性与其他相关的染色质重塑 ATP 酶（如 ACF 和 BRG1）不同，不会导致核小体完全破坏或失稳。相反，CHD5 可能以类似于其他重塑因子的方式启动重塑，但不会显著重新定位核小体。虽然相关因子 CHD4 显示出很强的 ATP 酶活性，但它不像 CHD5 那样有效地解开核小体。我们的发现增加了越来越多的证据，表明染色质重塑 ATP 酶在调节染色质结构方面具有多种作用。
