Beijing Institute of Ratiation Medicine, Department of Biotechnology.
Beijing Institute of Radiation Medicine.
Brief Bioinform. 2021 May 20;22(3). doi: 10.1093/bib/bbaa210.
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.
拓扑关联域（TAD）是真核生物染色质结构的空间和功能单位。解释调控因子与 TAD 内染色质结构之间的相互作用对于理解基因表达的时空调控至关重要。然而，目前缺乏用于敏感描述 TAD 调控景观的计算指标。在这里，我们提出了开放染色质的空间密度（SDOC）度量标准，作为 TAD 内染色质状态和结构的定量测量。SDOC 灵敏地反映了 TAD 中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 富含被抑制的发育基因，而 SDOC 降低和 TAD 聚类的共同作用对应于基因抑制的最高水平。此外，我们揭示了一种普遍的偏好，即具有相似 SDOC 的 TAD 相互作用，这可能反映了染色质组织的原则。
