Shukla Shagun, Paul Somnath, Garcia Jeison, Zhong Yuan, Juste Sara Sanz, Beauchemin Karissa, Bartholomew Blaine
Department of Epigenetics and Molecular Carcinogenesis, UT MD Anderson Cancer Center, 1901 East Rd., Houston, TX 77054, USA.
Department of Internal Medicine, Division of Medical Genetics, McGovern Medical School, UT Health Science Center at Houston, 6431 Fannie St., Houston, TX 77030, USA.
Nucleic Acids Res. 2025 Jan 11;53(2). doi: 10.1093/nar/gkae1187.
The INO80 chromatin remodeler is a versatile enzyme capable of several functions, including spacing nucleosomes equal distances apart, precise positioning of nucleosomes based on DNA shape/sequence and exchanging histone dimers. Within INO80, the Arp5 subunit plays a central role in INO80 remodeling, evidenced by its interactions with the histone octamer, nucleosomal and extranucleosomal DNA, and its necessity in linking INO80's ATPase activity to nucleosome movement. We find two distinct regions of Arp5 binding near the acidic pocket of nucleosomes. One region has an arginine anchor that binds nucleosomes and is vital for INO80 mobilizing nucleosomes. The other region has a hydrophobic/acid patch of Leu and Asp that binds free histone H2A-H2B dimers. These two regions have different roles in remodeling nucleosomes as seen both in vitro and in vivo and the hydrophobic/acidic patch of Arp5 is likely needed for displacing DNA from the H2A-H2B surface and dimer exchange by INO80.
INO80染色质重塑酶是一种多功能酶，能够执行多种功能，包括将核小体等距离隔开、根据DNA形状/序列精确定位核小体以及交换组蛋白二聚体。在INO80中，Arp5亚基在INO80重塑中起核心作用，这一点可通过其与组蛋白八聚体、核小体和核小体外DNA的相互作用得到证明，并且它对于将INO80的ATP酶活性与核小体运动联系起来是必不可少的。我们发现在核小体酸性口袋附近有两个不同的Arp5结合区域。一个区域有一个结合核小体的精氨酸锚，对INO80移动核小体至关重要。另一个区域有一个由亮氨酸和天冬氨酸组成的疏水/酸性区域，可结合游离的组蛋白H2A-H2B二聚体。这两个区域在核小体重塑中具有不同作用，这在体外和体内实验中均有体现，并且Arp5的疏水/酸性区域可能是INO80将DNA从H2A-H2B表面置换下来以及进行二聚体交换所必需的。
