Chromatin three-dimensional (3D) organization inside the cell nucleus determines the separation of euchromatin and heterochromatin domains. Their segregation results in the definition of active and inactive chromatin compartments, whereby the local concentration of associated proteins, RNA and DNA results in the formation of distinct subnuclear structures. Thus, chromatin domains spatially confined in a specific 3D nuclear compartment are expected to share similar epigenetic features and biochemical properties, in terms of accessibility and solubility. Based on this rationale, we developed the 4f-SAMMY-seq to map euchromatin and heterochromatin based on their accessibility and solubility, starting from as little as 10 000 cells. Adopting a tailored bioinformatic data analysis approach we reconstruct also their 3D segregation in active and inactive chromatin compartments and sub-compartments, thus recapitulating the characteristic properties of distinct chromatin states. A key novelty of the new method is the capability to map both the linear segmentation of open and closed chromatin domains, as well as their compartmentalization in one single experiment.

中文翻译：

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染色质结构域的生化特性定义了基因组区室化


细胞核内的染色质三维​​ (3D) 组织决定了常染色质和异染色质域的分离。它们的分离导致了活性和非活性染色质区室的定义，从而相关蛋白质、RNA 和 DNA 的局部浓度导致了不同亚核结构的形成。因此，空间上限制在特定 3D 核区室中的染色质结构域在可及性和溶解性方面预计具有相似的表观遗传特征和生化特性。基于这一原理，我们开发了 4f-SAMMY-seq，根据常染色质和异染色质的可及性和溶解度，从少至 10 000 个细胞开始绘制常染色质和异染色质图谱。采用定制的生物信息学数据分析方法，我们还重建了它们在活性和非活性染色质区室和子区室中的 3D 分离，从而概括了不同染色质状态的特征特性。新方法的一个关键新颖之处是能够在一次实验中绘制开放和闭合染色质域的线性分割及其区室化。