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ZBTB17 (MIZ1) is important for the cardiac stress response and a novel candidate gene for cardiomyopathy and heart failure

Item Type:Article
Title:ZBTB17 (MIZ1) is important for the cardiac stress response and a novel candidate gene for cardiomyopathy and heart failure
Creators Name:Buyandelger, B. and Mansfield, C. and Kostin, S. and Choi, O. and Roberts, A.M. and Ware, J.S. and Mazzarotto, F. and Pesce, F. and Buchan, R. and Isaacson, R.L. and Vouffo, J. and Gunkel, S. and Knoell, G. and McSweeney, S.J. and Wei, H. and Perrot, A. and Pfeiffer, C. and Toliat, M.R. and Ilieva, K. and Krysztofinska, E. and López-Olañeta, M.M. and Gómez-Salinero, J.M. and Schmidt, A. and Ng, K.E. and Teucher, N. and Chen, J. and Teichmann, M. and Eilers, M. and Haverkamp, W. and Regitz-Zagrosek, V. and Hasenfuss, G. and Braun, T. and Pennell, D.J. and Gould, I. and Barton, P.J.R. and Lara-Pezzi, E. and Schäfer, S. and Hübner, N. and Felkin, L.E. and O'Regan, D.P. and Petretto, E. and Brand, T. and Milting, H. and Nürnberg, P. and Schneider, M.D. and Prasad, S. and Knöll, R.
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 (CSRP3), a known cardiomyopathy gene, in a yeast two-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 which may play a role as a novel cardiomyopathy gene.
Keywords:Heart Failure, Cardiomyopathy, Genetics, Animal Models, Animals, Mice, Rats
Source:Circulation Cardiovascular Genetics
Publisher:Lippincott Williams & Wilkins
Page Range:643-652
Date:October 2015
Additional Information:Copyright © 2015 American Heart Association, Inc.
Official Publication:https://doi.org/10.1161/CIRCGENETICS.113.000690
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