Department of Early Discovery Biochemistry, Genentech, Inc., South San Francisco, CA, USA
Department of Structural Biology, Genentech, Inc., South San Francisco, CA, USA.
EMBO Rep. 2017 Oct;18(10):1697-1706. doi: 10.15252/embr.201744011. Epub 2017 Aug 11.
ISWI chromatin remodelers mobilize nucleosomes to control DNA accessibility. Complexes isolated to date pair one of six regulatory subunits with one of two highly similar ATPases. However, we find that each endogenously expressed ATPase co-purifies with every regulatory subunit, substantially increasing the diversity of ISWI complexes, and we additionally identify BAZ2B as a novel, seventh regulatory subunit. Through reconstitution of catalytically active human ISWI complexes, we demonstrate that the new interactions described here are stable and direct. Finally, we profile the nucleosome remodeling functions of the now expanded family of ISWI chromatin remodelers. By revealing the combinatorial nature of ISWI complexes, we provide a basis for better understanding ISWI function in normal settings and disease.
ISWI 染色质重塑酶可将核小体移动以控制 DNA 的可及性。迄今为止分离到的复合物将六种调节亚基之一与两种高度相似的 ATP 酶之一配对。然而,我们发现每个内源性表达的 ATP 酶都与每个调节亚基共纯化,这大大增加了 ISWI 复合物的多样性,并且我们还鉴定了 BAZ2B 作为一种新的第七个调节亚基。通过重建具有催化活性的人源 ISWI 复合物,我们证明了此处描述的新相互作用是稳定且直接的。最后,我们对现在扩展的 ISWI 染色质重塑酶家族的核小体重塑功能进行了分析。通过揭示 ISWI 复合物的组合性质,我们为更好地理解 ISWI 在正常环境和疾病中的功能提供了基础。