Interrogating cell type-specific cooperation of transcriptional regulators in 3D chromatin

• DOI: 10.1016/j.isci.2021.103468
• Publication Date: 2021-11-18T02:06:45Z
• Authors: Xianfu Yi; Zhanye Zheng; Hang Xu; Yao Zhou; Dandan Huang; Jianhua Wang; Xiangling Feng; Ke Zhao; Xutong Fan; Shijie Zhang; Xiaobao Dong; Zhao Wang; Yujun Shen; Hui Cheng; Lei Shi; Mulin Jun Li
• Keywords: ChIA-PET; Scaffold/matrix attachment region; Gene regulatory network; Cell type; Footprinting

Context-specific activities of transcription regulators (TRs) in the nucleus modulate spatiotemporal gene expression precisely. Using largest ChIP-seq data and chromatin loops human K562 cell line, we initially interrogated TR cooperation 3D via a graphical model revealed many known novel TRs manipulating context-specific pathways. To explore across broad tissue/cell types, systematically leveraged large-scale open profiles, computational footprinting, high-resolution interactions to investigate type-specific cooperation. We first delineated landscape 40 types. Network modularity analyses uncovered commonality specificity different conditions. also demonstrated that information can better interpret disease-causal variants identified by genome-wide association studies recapitulate states during neural development. Our study characterizes shared unique patterns associated with type regulation chromatin.