TY - JOUR A1 - Nordin, Anna A1 - Chakraborty, Chaitali A1 - Jonasson, Mattias A1 - Dano, Orgena A1 - Zambanini, Gianluca A1 - Pagella, Pierfrancesco A1 - Remeseiro, Silvia A1 - Cantù, Claudio T1 - Wnt signaling activation induces CTCF binding and loop formation at cis-regulatory elements of target genes Y1 - 2025/08/01 JF - Genome Research JO - Genome Research SP - 1701 EP - 1716 DO - 10.1101/gr.279684.124 VL - 35 IS - 8 UR - http://genome.cshlp.org/content/35/8/1701.abstract N2 - Wnt signaling plays a pivotal role during development and homeostasis. Upon pathway activation, CTNNB1 (also known as beta-catenin) drives the expression of target genes from regulatory regions bound by TCF/LEF transcription factors. Gene regulation, however, entails the interplay between sequence information and 3D genome structure, yet the impact of Wnt signaling on genome structure has been poorly explored. Here, we investigate how Wnt signaling influences CTCF and cohesin, key regulators of 3D genome organization. We identify a series of novel CTCF binding sites that emerge upon Wnt stimulation: CTCF Redistributions Under Wnt (RUW). RUW sites are characterized by CTCF, cohesin, and TCF/LEF occupancy, and are dependent on beta-catenin. Beta-catenin and CTCF colocalize upon pathway activation, and disruption of selected binding sites perturbs target gene regulation. Moreover, Wnt signaling reorganizes the 3D genome as evidenced by genome-wide alterations in CTCF-bound loops. This work reveals a previously unexplored role for CTCF in the regulation of Wnt signaling. ER -