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

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

Automated summary

This study revealed the precise modulation of gene expression by context-specific activities of transcription regulators in the nucleus through large-scale data analysis. Exploring across different tissues and cell types, it discovered both common and specific patterns of cooperation among transcription regulators, providing new insights into cell type-specific gene regulation.