RT Journal
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
JF Genome Research 
JO Genome Research 
YR 2025 
FD August 01 
VO 35 
IS 8 
SP 1701 
OP 1716 
DO 10.1101/gr.279684.124 
UL http://genome.cshlp.org/content/35/8/1701.abstract 
AB 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.