Nodelman Ilana M, Folkwein Heather J, Glime Wesley S, Armache Jean-Paul, Bowman Gregory D
Thomas C. Jenkins Department of Biophysics, Johns Hopkins University, Baltimore, MD, USA.
Department of Biochemistry and Molecular Biology and the Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA, USA.
Nat Struct Mol Biol. 2025 May 28. doi: 10.1038/s41594-025-01556-y.
The Chd1 chromatin remodeler repositions nucleosomes into evenly spaced arrays, a characteristic of most eukaryotic genes. Here we show that the yeast Chd1 remodeler requires two activating segments to distort nucleosomal DNA into an A-form-like conformation, a critical first step in nucleosome sliding. As shown by cryo-electron microscopy, these two activating segments together pack against the ATPase motor, where they are poised to stabilize the central ATPase cleft. These activating elements contact the ATPase at locations that are incompatible with binding of NegC, an autoinhibitory segment located between the two activators. NegC inhibits sliding by antagonizing the activators through steric competition and constraining activator placement, giving rise to directional nucleosome sliding. Given that activator reinforcement of the ATPase cleft is needed for DNA distortion, this first step in remodeling appears to provide a natural checkpoint for regulation of chromatin remodeler activity.
Chd1染色质重塑因子将核小体重新定位成均匀间隔的阵列，这是大多数真核基因的一个特征。我们在此表明，酵母Chd1重塑因子需要两个激活片段将核小体DNA扭曲成类似A-DNA的构象，这是核小体滑动的关键第一步。冷冻电子显微镜显示，这两个激活片段一起靠在ATP酶马达上，它们在那里准备稳定中央ATP酶裂缝。这些激活元件在与NegC结合不相容的位置接触ATP酶，NegC是位于两个激活剂之间的一个自抑制片段。NegC通过空间竞争拮抗激活剂并限制激活剂的位置来抑制滑动，从而产生定向核小体滑动。鉴于DNA扭曲需要激活剂加强ATP酶裂缝，重塑的这第一步似乎为染色质重塑因子活性的调节提供了一个天然检查点。
