Topologically associated domains (TADs) are spatial and functional units of metazoan chromatin structure. Interpretation of the interplay between regulatory factors and chromatin structure within TADs is crucial to understand the spatial and temporal regulation of gene expression. However, a computational metric for the sensitive characterization of TAD regulatory landscape is lacking. Here, we present the spatial density of open chromatin (SDOC) metric as a quantitative measurement of intra-TAD chromatin state and structure. SDOC sensitively reflects epigenetic properties and gene transcriptional activity in TADs. During mouse T-cell development, we found that TADs with decreased SDOC are enriched in repressed developmental genes, and the joint effect of SDOC-decreasing and TAD clustering corresponds to the highest level of gene repression. In addition, we revealed a pervasive preference for TADs with similar SDOC to interact with each other, which may reflect the principle of chromatin organization.

中文翻译：

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开放染色质的空间密度：拓扑相关域功能表征的有效指标

拓扑相关域 (TAD) 是后生动物染色质结构的空间和功能单元。解释 TAD 内调节因子和染色质结构之间的相互作用对于理解基因表达的空间和时间调节至关重要。然而，缺乏对 TAD 监管环境敏感特征的计算指标。在这里，我们将开放染色质 (SDOC) 度量的空间密度作为 TAD 内染色质状态和结构的定量测量。SDOC 敏感地反映了 TAD 的表观遗传特性和基因转录活性。在小鼠 T 细胞发育过程中，我们发现 SDOC 降低的 TAD 富含受抑制的发育基因，并且 SDOC 降低和 TAD 聚类的联合效应对应于最高水平的基因抑制。