# CTCF Mediates the Cis-Regulatory Hubs in Mouse Hearts

## TL;DR

This study shows that CTCF plays a key role in organizing gene regulatory networks in mouse hearts by influencing enhancer-promoter interactions and cis-regulatory hubs.

## Contribution

The study reveals how CTCF loss alters enhancer rankings, reduces CRH numbers, and increases CRH size and TAD boundary crossing in mouse hearts.

## Key findings

- CTCF loss reorganizes enhancer rankings in mouse hearts.
- CRH numbers decrease and their size increases with CTCF loss.
- More CRHs cross TAD boundaries when CTCF is absent.

## Abstract

The 3D chromatin architecture establishes a complex network of genes and regulatory elements necessary for transcriptomic regulation in development and disease. This network can be modeled by cis-regulatory hubs (CRH), which underscore the local functional interactions between enhancers and promoter regions and differ from other higher-order chromatin structures such as topologically associated domains (TAD). The activity-by-contact (ABC) model of enhancer–promoter regulation has been recently used in the identification of these CRHs, but little is known about the role of transcription factor CCTC binding factor (CTCF) on ABC scores and their consequent impact on CRHs. Here, we show that the loss of CTCF leads to a reorganization of the ABC-derived rankings of putative enhancers in the mouse heart, a global reduction in the total number of CRHs and an increase in the size of CRHs. Furthermore, CTCF loss leads to a higher percentage of CRHs that cross TAD boundaries. These results provide additional evidence to support the importance of CTCF in forming the regulatory networks necessary for gene regulation.