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

Byambajav Buyandelger; Catherine Mansfield; Sawa Kostin; Onjee Choi; Angharad M Roberts; James S Ware; Francesco Mazzarotto; Francesco Pesce; Rachel Buchan; Rivka Isaacson; Josee Vouffo; Sylvia Gunkel; Gudrun Knöll; Sara J McSweeney; Heming Wei; Andreas Perrot; Conny Pfeiffer; Mohammad Reza Toliat; Kristina Ilieva; Ewelina Krysztofinska; Marina M López-Olañeta; Jesús M Gómez-Salinero; Albrecht Schmidt; Keat-Eng Ng; Niels Teucher; Ju Chen; Martin Teichmann; Martin Eilers; Wilhelm Haverkamp; Vera Regitz-Zagrosek; Gerd Hasenfuss; Thomas Braun; Dudley J Pennell; Ian Gould; Paul J R Barton; Enrique Lara-Pezzi; Sebastian Schafer; Norbert Hübner; Leanne E Felkin; Declan P O'Regan; Enrico Petretto; Thomas Brand; Hendrik Milting; Peter Nürnberg; Michael D Schneider; Sanjay Prasad; Ralph Knöll

doi:10.1161/CIRCGENETICS.113.000690

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

Byambajav Buyandelger, Catherine Mansfield, Sawa Kostin, Onjee Choi, Angharad M Roberts, James S Ware, Francesco Mazzarotto, Francesco Pesce, Rachel Buchan, Rivka Isaacson, Josee Vouffo, Sylvia Gunkel, Gudrun Knöll, Sara J McSweeney, Heming Wei, Andreas Perrot, Conny Pfeiffer, Mohammad Reza Toliat, Kristina Ilieva, Ewelina KrysztofinskaMarina M López-Olañeta, Jesús M Gómez-Salinero, Albrecht Schmidt, Keat-Eng Ng, Niels Teucher, Ju Chen, Martin Teichmann, Martin Eilers, Wilhelm Haverkamp, Vera Regitz-Zagrosek, Gerd Hasenfuss, Thomas Braun, Dudley J Pennell, Ian Gould, Paul J R Barton, Enrique Lara-Pezzi, Sebastian Schafer, Norbert Hübner, Leanne E Felkin, Declan P O'Regan, Enrico Petretto, Thomas Brand, Hendrik Milting, Peter Nürnberg, Michael D Schneider, Sanjay Prasad, Ralph Knöll

Research output: Contribution to journal › Article › peer-review

12 Citations (Scopus)

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.

Original language	English
Pages (from-to)	643-652
Number of pages	9
Journal	Circulation-Cardiovascular Genetics
Volume	8
Issue number	5
Early online date	14 Jul 2015
DOIs	https://doi.org/10.1161/CIRCGENETICS.113.000690
Publication status	Published - Oct 2015

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Buyandelger, B., Mansfield, C., Kostin, S., Choi, O., Roberts, A. M., Ware, J. S., Mazzarotto, F., Pesce, F., Buchan, R., Isaacson, R., Vouffo, J., Gunkel, S., Knöll, G., McSweeney, S. J., Wei, H., Perrot, A., Pfeiffer, C., Toliat, M. R., Ilieva, K., ... Knöll, R. (2015). ZBTB17 (MIZ1) Is Important for the Cardiac Stress Response and a Novel Candidate Gene for Cardiomyopathy and Heart Failure. Circulation-Cardiovascular Genetics, 8(5), 643-652. https://doi.org/10.1161/CIRCGENETICS.113.000690

@article{28bc2996c77a4107b911baefcb90c12a,

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

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.",

author = "Byambajav Buyandelger and Catherine Mansfield and Sawa Kostin and Onjee Choi and Roberts, {Angharad M} and Ware, {James S} and Francesco Mazzarotto and Francesco Pesce and Rachel Buchan and Rivka Isaacson and Josee Vouffo and Sylvia Gunkel and Gudrun Kn{\"o}ll and McSweeney, {Sara J} and Heming Wei and Andreas Perrot and Conny Pfeiffer and Toliat, {Mohammad Reza} and Kristina Ilieva and Ewelina Krysztofinska and L{\'o}pez-Ola{\~n}eta, {Marina M} and G{\'o}mez-Salinero, {Jes{\'u}s M} and Albrecht Schmidt and Keat-Eng Ng and Niels Teucher and Ju Chen and Martin Teichmann and Martin Eilers and Wilhelm Haverkamp and Vera Regitz-Zagrosek and Gerd Hasenfuss and Thomas Braun and Pennell, {Dudley J} and Ian Gould and Barton, {Paul J R} and Enrique Lara-Pezzi and Sebastian Schafer and Norbert H{\"u}bner and Felkin, {Leanne E} and O'Regan, {Declan P} and Enrico Petretto and Thomas Brand and Hendrik Milting and Peter N{\"u}rnberg and Schneider, {Michael D} and Sanjay Prasad and Ralph Kn{\"o}ll",

year = "2015",

month = oct,

doi = "10.1161/CIRCGENETICS.113.000690",

language = "English",

volume = "8",

pages = "643--652",

journal = "Circulation-Cardiovascular Genetics",

issn = "1942-325X",

publisher = "American Heart Association, Inc.",

number = "5",

}

Buyandelger, B, Mansfield, C, Kostin, S, Choi, O, Roberts, AM, Ware, JS, Mazzarotto, F, Pesce, F, Buchan, R, Isaacson, R, Vouffo, J, Gunkel, S, Knöll, G, McSweeney, SJ, Wei, H, Perrot, A, Pfeiffer, C, Toliat, MR, Ilieva, K, Krysztofinska, E, López-Olañeta, MM, Gómez-Salinero, JM, Schmidt, A, Ng, K-E, Teucher, N, Chen, J, Teichmann, M, Eilers, M, Haverkamp, W, Regitz-Zagrosek, V, Hasenfuss, G, Braun, T, Pennell, DJ, Gould, I, Barton, PJR, Lara-Pezzi, E, Schafer, S, Hübner, N, Felkin, LE, O'Regan, DP, Petretto, E, Brand, T, Milting, H, Nürnberg, P, Schneider, MD, Prasad, S & Knöll, R 2015, 'ZBTB17 (MIZ1) Is Important for the Cardiac Stress Response and a Novel Candidate Gene for Cardiomyopathy and Heart Failure', Circulation-Cardiovascular Genetics, vol. 8, no. 5, pp. 643-652. https://doi.org/10.1161/CIRCGENETICS.113.000690

TY - JOUR

T1 - ZBTB17 (MIZ1) Is Important for the Cardiac Stress Response and a Novel Candidate Gene for Cardiomyopathy and Heart Failure

AU - Buyandelger, Byambajav

AU - Mansfield, Catherine

AU - Kostin, Sawa

AU - Choi, Onjee

AU - Roberts, Angharad M

AU - Ware, James S

AU - Mazzarotto, Francesco

AU - Pesce, Francesco

AU - Buchan, Rachel

AU - Isaacson, Rivka

AU - Vouffo, Josee

AU - Gunkel, Sylvia

AU - Knöll, Gudrun

AU - McSweeney, Sara J

AU - Wei, Heming

AU - Perrot, Andreas

AU - Pfeiffer, Conny

AU - Toliat, Mohammad Reza

AU - Ilieva, Kristina

AU - Krysztofinska, Ewelina

AU - López-Olañeta, Marina M

AU - Gómez-Salinero, Jesús M

AU - Schmidt, Albrecht

AU - Ng, Keat-Eng

AU - Teucher, Niels

AU - Chen, Ju

AU - Teichmann, Martin

AU - Eilers, Martin

AU - Haverkamp, Wilhelm

AU - Regitz-Zagrosek, Vera

AU - Hasenfuss, Gerd

AU - Braun, Thomas

AU - Pennell, Dudley J

AU - Gould, Ian

AU - Barton, Paul J R

AU - Lara-Pezzi, Enrique

AU - Schafer, Sebastian

AU - Hübner, Norbert

AU - Felkin, Leanne E

AU - O'Regan, Declan P

AU - Petretto, Enrico

AU - Brand, Thomas

AU - Milting, Hendrik

AU - Nürnberg, Peter

AU - Schneider, Michael D

AU - Prasad, Sanjay

AU - Knöll, Ralph

PY - 2015/10

Y1 - 2015/10

N2 - 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.

AB - 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.

U2 - 10.1161/CIRCGENETICS.113.000690

DO - 10.1161/CIRCGENETICS.113.000690

M3 - Article

C2 - 26175529

SN - 1942-325X

VL - 8

SP - 643

EP - 652

JO - Circulation-Cardiovascular Genetics

JF - Circulation-Cardiovascular Genetics

IS - 5

ER -

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

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