ZBTB17 (MIZ1) Is Important for the Cardiac Stress Response and a Novel Candidate Gene for Cardiomyopathy and Heart Failure. (October 2015)

• Record Type: Journal Article
• Authors: Buyandelger, Byambajav; Mansfield, Catherine; Kostin, Sawa; Choi, Onjee; Roberts, Angharad M.; Ware, James S.; Mazzarotto, Francesco; Pesce, Francesco; Buchan, Rachel; Isaacson, Rivka L.; Vouffo, Josée; Gunkel, Sylvia; Knöll, Gudrun; McSweeney, Sara J.; Wei, Heming; Perrot, Andreas; Pfeiffer, Conny; Toliat, Mohammad Reza; Ilieva, Kristina; Krysztofinska, Ewelina; López-Olañeta, Marina M.; Gómez-Salinero, Jesús M.; Schmidt, Albrecht; Ng, Keat-Eng; Teucher, Niels; Chen, Ju; Teichmann, Martin; Eilers, Martin; Haverkamp, Wilhelm; Regitz-Zagrosek, Vera; Hasenfuss, Gerd; Braun, Thomas; Pennell, Dudley J.; Gould, Ian; Barton, Paul J.R.; Lara-Pezzi, Enrique; Schäfer, Sebastian; Hübner, Norbert; Felkin, Leanne E.; O'Regan, Declan P.; Brand, Thomas; Milting, Hendrik; Nürnberg, Peter; Schneider, Michael D.; Prasad, Sanjay; Petretto, Enrico; Knöll, Ralph;
• Is Part Of: Circulation. Volume 8:Number 5(2015)
• Publication Date: 2015-10
• Subjects: cardiomyopathies -- genetics -- heart failure -- models, animal -- mutation; Arrhythmia -- Periodicals; Heart -- Electric properties -- Periodicals; 616.1042
• DOI: 10.1161/CIRCGENETICS.113.000690
• Languages: English
• ISSNs: 1942-325X

Abstract

Abstract : Background—: Mutations in sarcomeric and cytoskeletal proteins are a major cause of hereditary cardiomyopathies, but our knowledge remains incomplete as to how the genetic defects execute their effects. Methods and Results—: We used cysteine and glycine-rich protein 3, a known cardiomyopathy gene, in a yeast 2-hybrid screen and identified zinc-finger and BTB domain-containing protein 17 ( ZBTB17 ) as a novel interacting partner. ZBTB17 is a transcription factor that contains the peak association signal (rs10927875) at the replicated 1p36 cardiomyopathy locus. ZBTB17 expression protected cardiac myocytes from apoptosis in vitro and in a mouse model with cardiac myocyte–specific deletion of Zbtb17, which develops cardiomyopathy and fibrosis after biomechanical stress. ZBTB17 also regulated cardiac myocyte hypertrophy in vitro and in vivo in a calcineurin-dependent manner. Conclusions—: We revealed new functions for ZBTB17 in the heart, a transcription factor that may play a role as a novel cardiomyopathy gene. Abstract : Supplemental Digital Content is available in the text.