A context-specific cardiac Beta-catenin and GATA4 interaction influences TCF7L2 occupancy and remodels chromatin driving disease progression in the adult heart

https://sfb1002.med.uni-goettingen.de/ (Research Data Platform) https://gepris.dfg.de/gepris/projekt/193793266?language=en (DFG Gepris entry) With a prevalence of between two and four percent, heart failure remains one of the most common diseases in Europe. Although tremendous progress has been made in its treatment, the morbidity and mortality of affected patients remains high. Advanced heart failure can still only be treated palliatively.We define modulatory units as cell-based and/or genetic ...

https://gepris.dfg.de/gepris/projekt/318243743 Title: Wnt/beta-catenin/TCF-dependent transcriptional regulation in heart failure (Wnt/beta-catenin/TCF-abhängige Transkriptionsregulation in der Herzinsuffizienz) Wnt/ß-catenin activation results in the development of cardiac dysfunction. In this project, the hypothesis will be tested that enhanced Wnt/ß-catenin activity triggers a cell-specific gene expression programs in cardiomyocytes (CM) and cardiac fibroblasts (FB), which contribute to ...

Activation of the evolutionarily conserved, developmental Wnt pathway has been reported during maladaptive cardiac remodeling. Although the function of Wnt-transcriptional activation in development is well described, the consequences of Wnt pathway activation, as well as its cardiac-specific regulatory role in the adult heart, is largely unknown. We show that β-catenin and Transcription factor 7-like 2 (TCF7L2), the main nuclear components of the Wnt-transcriptional cascade, and their transcriptional ...

Summary: Activation of the evolutionarily conserved, developmental Wnt pathway has been reported during maladaptive cardiac remodeling. Although the function of Wnt-transcriptional activation in development is well described, the consequences of Wnt pathway activation, as well as its cardiac-specific regulatory role in the adult heart, is largely unknown. We show that β-catenin and Transcription factor 7-like 2 (TCF7L2), the main nuclear components of the Wnt-transcriptional cascade, and their ...

Transaortic constriction (TAC) was done in 12-weeks-old mice. Pre-anesthetic and anesthetic agents are listed in Supplemental Table S2. The intervention was performed by tying a braided 5–0 polyviolene suture (Hugo Sachs Electronik) ligature around the aorta and a blunted 26-gauge needle and subsequent removal of the needle. For sham controls, the suture was not tied. To determine the level of pressure overload by aortic ligation, a high frequency Doppler probe was used to measure the ratio between ...