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

Circ Cardiovasc Genet. 2015 Oct;8(5):643-52. doi: 10.1161/CIRCGENETICS.113.000690. Epub 2015 Jul 14.


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.

Keywords: cardiomyopathies; genetics; heart failure; models, animal; mutation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiomyopathies / genetics*
  • DNA-Binding Proteins
  • Heart / physiology
  • Heart Failure / genetics*
  • Humans
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / physiology
  • LIM Domain Proteins / genetics
  • LIM Domain Proteins / metabolism
  • Mice
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / physiology
  • Protein Inhibitors of Activated STAT / genetics
  • Protein Inhibitors of Activated STAT / physiology
  • Rats
  • Stress, Physiological
  • Tissue Culture Techniques
  • Ubiquitin-Protein Ligases


  • DNA-Binding Proteins
  • Kruppel-Like Transcription Factors
  • LIM Domain Proteins
  • Muscle Proteins
  • Nuclear Proteins
  • Protein Inhibitors of Activated STAT
  • ZBTB17 protein, human
  • cysteine and glycine-rich protein 3
  • Miz1 protein, mouse
  • Ubiquitin-Protein Ligases
  • Pias2 protein, rat