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

2015 | journal article; research paper. A publication with affiliation to the University of Göttingen.

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​ZBTB17 (MIZ1) Is Important for the Cardiac Stress Response and a Novel Candidate Gene for Cardiomyopathy and Heart Failure​
Buyandelger, B.; Mansfield, C.; Kostin, S.; Choi, O.; Roberts, A. M.; Ware, J. S. & Mazzarotto, F. et al.​ (2015) 
Circulation: Cardiovascular Genetics8(5) pp. 643​-652​.​ DOI: https://doi.org/10.1161/CIRCGENETICS.113.000690 

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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, Josee; Gunkel, Sylvia; Knoll, Gudrun; McSweeney, Sara J.; Wei, Heming; Perrot, Andreas; Pfeiffer, Conny; Toliat, Mohammad Reza; Ilieva, Kristina; Krysztofinska, Ewelina; Lopez-Olaneta, Marina M.; Gomez-Salinero, Jesus 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; Schaefer, Sebastian ; Hübner, Norbert; Felkin, Leanne E.; O'Regan, D. P.; Brand, Thomas; Milting, Hendrik; Nürnberg, Peter; Schneider, Michael D.; Prasad, Sanjay; Petretto, Enrico; Knoll, Ralph
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.
Issue Date
2015
Journal
Circulation: Cardiovascular Genetics 
ISSN
1942-325X
eISSN
1942-3268

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