Nucleosome density shapes kilobase-scale regulation by a mammalian chromatin remodeler.
Nucleosome density shapes kilobase-scale regulation by a mammalian chromatin remodeler.
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DOI：
10.1038/s41594-023-01093-6
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发表时间：
2023-10
影响因子：
16.8
通讯作者：
Ramani, Vijay
中科院分区：
文献类型：
--
作者：
Abdulhay, Nour J.;Hsieh, Laura J.;Mcnally, Colin P.;Ostrowski, Megan S.;Moore, Camille M.;Ketavarapu, Mythili;Kasinathan, Sivakanthan;Nanda, Arjun S.;Wu, Ke;Chio, Un Seng;Zhou, Ziling;Goodarzi, Hani;Narlikar, Geeta J.;Ramani, Vijay
几乎所有重要的核过程都作用于包装成核小体阵列的 DNA。然而，我们对这些过程（例如 DNA 复制、RNA 转录、染色质挤出和核小体重塑）如何在单个染色质阵列上发生的理解仍未解决。在这里，为了解决这一缺陷，我们提出了 SAMOSA-ChAAT：一种大规模多重单分子足迹方法，用于绘制几乎任何染色质相关反应的单个重构染色质模板的一级结构。我们应用这种方法来区分通过基本模仿开关 (ISWI) ATPase SNF2h 进行染色质重塑的竞争模型：核小体密度依赖性间距与固定接头长度核小体夹紧。首先，我们在小鼠胚胎干细胞中进行体内单分子核小体足迹，发现 ISWI 催化的核小体间距与特定表观基因组域的潜在核小体密度相关。为了建立因果关系，我们应用 SAMOSA-ChAAT 以单分子分辨率量化 ISWI ATPase SNF2h 及其亲本复合物 ACF 在不同核小体密度的重构核小体阵列上的活性。我们证明 ISWI 重塑器作为密度依赖性、长度感应核小体滑块运行，其编程 DNA 可及性的能力由单分子核小体密度决定。我们提出，ISWI 复合物长期观察到的、特定环境的调节作用可以部分地通过表观基因组域内核小体密度的感知来解释。更一般地说，我们的方法有望对塑造核生理学的基本过程提供分子精确的视图。作者在此提出了 SAMOSA-ChAAT，这是一种以高通量和大规模解决染色质相互作用蛋白如何重组单个染色质纤维的方法。他们提供的证据表明，模拟开关家族重塑酶可感知核小体密度，以编程单个分子上的核小体间距。
Nearly all essential nuclear processes act on DNA packaged into arrays of nucleosomes. However, our understanding of how these processes (for example, DNA replication, RNA transcription, chromatin extrusion and nucleosome remodeling) occur on individual chromatin arrays remains unresolved. Here, to address this deficit, we present SAMOSA-ChAAT: a massively multiplex single-molecule footprinting approach to map the primary structure of individual, reconstituted chromatin templates subject to virtually any chromatin-associated reaction. We apply this method to distinguish between competing models for chromatin remodeling by the essential imitation switch (ISWI) ATPase SNF2h: nucleosome-density-dependent spacing versus fixed-linker-length nucleosome clamping. First, we perform in vivo single-molecule nucleosome footprinting in murine embryonic stem cells, to discover that ISWI-catalyzed nucleosome spacing correlates with the underlying nucleosome density of specific epigenomic domains. To establish causality, we apply SAMOSA-ChAAT to quantify the activities of ISWI ATPase SNF2h and its parent complex ACF on reconstituted nucleosomal arrays of varying nucleosome density, at single-molecule resolution. We demonstrate that ISWI remodelers operate as density-dependent, length-sensing nucleosome sliders, whose ability to program DNA accessibility is dictated by single-molecule nucleosome density. We propose that the long-observed, context-specific regulatory effects of ISWI complexes can be explained in part by the sensing of nucleosome density within epigenomic domains. More generally, our approach promises molecule-precise views of the essential processes that shape nuclear physiology. Here authors present SAMOSA-ChAAT, a method for resolving how chromatin-interacting proteins restructure individual chromatin fibers, in high throughput and at scale. They provide evidence that the imitation switch family remodeling enzymes sense nucleosome density to program internucleosomal spacing on individual molecules.
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影响因子：
46.9
作者：
Becht, Etienne;McInnes, Leland;Newell, Evan W.
通讯作者：
Newell, Evan W.
ISWI染色质重塑器感知核小体修饰以确定底物偏好。
影响因子：
64.8
作者：
Dann GP;Liszczak GP;Bagert JD;Müller MM;Nguyen UTT;Wojcik F;Brown ZZ;Bos J;Panchenko T;Pihl R;Pollock SB;Diehl KL;Allis CD;Muir TW
通讯作者：
Muir TW
影响因子：
16
作者：
Dechassa ML;Sabri A;Pondugula S;Kassabov SR;Chatterjee N;Kladde MP;Bartholomew B
通讯作者：
Bartholomew B
影响因子：
16
作者：
Grüne, T;Brzeski, J;Müller, CW
通讯作者：
Müller, CW
影响因子：
16
作者：
Brahma, Sandipan;Henikoff, Steven
通讯作者：
Henikoff, Steven