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

Tools

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., Mansfield, C., Kostin, S., Choi, O., Roberts, A.M., Ware, J.S., Mazzarotto, F., Pesce, F., Buchan, R., Isaacson, R.L., Vouffo, J., Gunkel, S., Knoell, G., McSweeney, S.J., Wei, H., Perrot, A., Pfeiffer, C., Toliat, M.R., Ilieva, K., Krysztofinska, E., López-Olañeta, M.M., Gómez-Salinero, J.M., Schmidt, A., Ng, K.E., Teucher, N., Chen, J., Teichmann, M., Eilers, M., Haverkamp, W., Regitz-Zagrosek, V., Hasenfuss, G., Braun, T., Pennell, D.J., Gould, I., Barton, P.J.R., Lara-Pezzi, E., Schäfer, S., Hübner, N., Felkin, L.E., O'Regan, D.P., Petretto, E., Brand, T., Milting, H., Nürnberg, P., Schneider, M.D., 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
ISSN:	1942-325X
Publisher:	Lippincott Williams & Wilkins
Volume:	8
Number:	5
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
External Fulltext:	View full text on external repository or document server
PubMed:	View item in PubMed

Repository Staff Only: item control page