Transcription factors organize into functional groups on the linear genome and in 3D chromatin

• DOI: 10.1016/j.heliyon.2023.e18211
• Publication Date: 2023-07-17T16:19:25Z
• Authors: Rakesh Netha Vadnala; Sridhar Hannenhalli; Leelavati Narlikar; Rahul Siddharthan
• Keywords: Scaffold/matrix attachment region; Transcription

Transcription factors (TFs) and their binding sites have evolved to interact cooperatively or competitively with each other. Here we examine in detail, across multiple cell lines, such cooperation competition among TFs both sequential spatial proximity (using chromatin conformation capture assays), considering vivo data as well TF motifs DNA. We ascertain significantly co-occurring ("attractive") avoiding ("repulsive") pairs using robust randomized models that retain the essential characteristics of experimental data. Across human lines organize into two groups, intra-group attraction inter-group repulsion. This is true for proximity, sequence motifs. Attractive exhibit more physical interactions suggesting an underlying mechanism. The groups differ genomic network properties, function-while one group regulates housekeeping function, other potentially lineage-specific functions, are disrupted cancer. Weaker tend occur spatially interacting regions genome. Our results suggest a complex pattern cooperativity has genome support functions.