Nucleosome Spacing Generated by ISWI and CHD1 Remodelers Is Constant Regardless of Nucleosome Density
Nucleosome Spacing Generated by ISWI and CHD1 Remodelers Is Constant Regardless of Nucleosome Density
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DOI：
10.1128/mcb.01070-14
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发表时间：
2015-05-01
影响因子：
5.3
通讯作者：
Korber, Philipp
中科院分区：
文献类型：
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作者：
Lieleg, Corinna;Ketterer, Philip;Korber, Philipp
规则排列的核小体是染色质的标志，但目前尚不清楚它们是如何产生的。最近在体外和体内的全基因组研究表明，即使在实验中降低了组蛋白的浓度，核小体间距也是恒定的。这与长期以来的假设相反，即核小体密度决定间距，并要求保持间距不变的因素与核小体密度无关。我们称之为夹紧活动。在这里，我们在一个纯化的系统中展示了ISWI型和CHD1型核小体重构器具有钳制活性，使得它们不仅产生规则间距的核小体阵列，而且无论核小体密度如何，都产生恒定的间距。这表明了一种功能上有吸引力的核小体相互作用，这种相互作用可以通过核小体-核小体接触直接介导，也可以通过重构体间接介导。没有HSS结构域的黑腹果蝇突变体ISWI没有可检测到的间隔活性，尽管它可以重塑和滑动核小体。这表明ISWI重构体在产生恒定间距方面的作用不仅是调节核小体滑动，它们还积极地促进了吸引人的相互作用。以绝对值来设置生理间隔是必要的附加因素。
Arrays of regularly spaced nucleosomes are a hallmark of chromatin, but it remains unclear how they are generated. Recent genome-wide studies, in vitro and in vivo, showed constant nucleosome spacing even if the histone concentration was experimentally reduced. This counters the long-held assumption that nucleosome density determines spacing and calls for factors keeping spacing constant regardless of nucleosome density. We call this a clamping activity. Here, we show in a purified system that ISWI- and CHD1-type nucleosome remodelers have a clamping activity such that they not only generate regularly spaced nucleosome arrays but also generate constant spacing regardless of nucleosome density. This points to a functionally attractive nucleosome interaction that could be mediated either directly by nucleosome-nucleosome contacts or indirectly through the remodelers. Mutant Drosophila melanogaster ISWI without the HAND-SANT-SLIDE (HSS) domain had no detectable spacing activity even though it is known to remodel and slide nucleosomes. This suggests that the role of ISWI remodelers in generating constant spacing is not just to mediate nucleosome sliding; they actively contribute to the attractive interaction. Additional factors are necessary to set physiological spacing in absolute terms.