Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China.
Changping Laboratory, Beijing, 102206, China.
Genome Res. 2023 Feb;33(2):247-260. doi: 10.1101/gr.277206.122. Epub 2023 Feb 24.
Dynamic chromatin structure acts as the regulator of transcription program in crucial processes including cancer and cell development, but a unified framework for characterizing chromatin structural evolution remains to be established. Here, we performed graph inferences on Hi-C data sets and derived the chromatin contact networks. We discovered significant decreases in information transmission efficiencies in chromatin of colorectal cancer (CRC) and T-cell acute lymphoblastic leukemia (T-ALL) compared to corresponding normal controls through graph statistics. Using network embedding in the Poincaré disk, the hierarchy depths of chromatin from CRC and T-ALL patients were found to be significantly shallower compared to their normal controls. A reverse trend of change in chromatin structure was observed during early embryo development. We found tissue-specific conservation of hierarchy order in chromatin contact networks. Our findings reveal the top-down hierarchy of chromatin organization, which is significantly attenuated in cancer.
动态染色质结构在包括癌症和细胞发育在内的关键过程中充当转录程序的调节剂，但仍需要建立一个统一的框架来描述染色质结构的演变。在这里，我们对 Hi-C 数据集进行了图推断，并得出了染色质相互作用网络。通过图统计，我们发现与相应的正常对照相比，结直肠癌 (CRC) 和 T 细胞急性淋巴细胞白血病 (T-ALL) 的染色质中信息传递效率显著降低。通过在庞加莱圆盘上的网络嵌入，我们发现 CRC 和 T-ALL 患者的染色质的层次深度明显比正常对照浅。在早期胚胎发育过程中，观察到染色质结构的反向变化趋势。我们发现染色质相互作用网络中的层次顺序具有组织特异性的保守性。我们的研究结果揭示了染色质组织的自上而下的层次结构，这种结构在癌症中明显减弱。
