# Systematic identification of cooperation between DNA binding proteins in 3D space

## TL;DR

This paper introduces a new method to identify how DNA-binding proteins work together in 3D space, revealing both known and new interactions that affect gene regulation.

## Contribution

The study introduces a novel network model integrating ChIP-seq and Hi-C data to systematically identify cis- and trans-cooperation between DNA-binding proteins.

## Key findings

- The method reveals cell-type-specific and independent cooperation between DNA-binding proteins.
- Many previously unknown trans-cooperations were identified in chromosomal loops.
- The software for analysis is publicly available for further research.

## Abstract

Cooperation between DNA-binding proteins (DBPs) such as transcription factors and chromatin remodeling enzymes plays a pivotal role in regulating gene expression and other biological processes. Such cooperation is often via interaction between DBPs that bind to loci located distal in the linear genome but close in the 3D space, referred as trans-cooperation. Due to the lack of 3D chromosomal structure, identification of DBP cooperation has been limited to those binding to neighbor regions in the linear genome, referred as cis-cooperation. Here we present the first study that integrates protein ChIP-seq and Hi-C data to systematically identify both cis- and trans-cooperation between DBPs. We developed a new network model that allows identification of cooperation between multiple DBPs and reveals cell type specific or independent regulations. Particularly interesting, we have retrieved many known and previously unknown trans-cooperation between DBPs in the chromosomal loops that may be a key factor for influencing 3D chromosomal structure. The software is available at http://wanglab.ucsd.edu/star/DBPnet/index.html.