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Hairy-related transcription factors inhibit GATA-dependent cardiac gene expression through a signal-responsive

Irfan S Kathiriya1, Isabelle N King, Masao Murakami

  • 1Department of Molecular Biology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9148, USA.

The Journal of Biological Chemistry
|October 16, 2004
PubMed

Insights

Hairy-related transcription factors (HRT) repress cardiac gene expression by blocking GATA factors. Signaling pathways can modulate this HRT-GATA interaction, impacting cardiac gene regulation.

Area of Science:

  • Molecular Biology
  • Cardiovascular Biology
  • Gene Regulation

Background:

  • Transcription factors orchestrate gene expression crucial for cardiac development and disease.
  • Hairy-related transcription factors (HRT) are repressors abundant in the cardiovascular system.
  • The interaction of HRT proteins with cardiac transcriptional activators was previously unknown.

Purpose of the Study:

  • To investigate whether HRT proteins modulate gene expression driven by cardiac transcriptional activators.
  • To elucidate the mechanism by which HRT proteins affect cardiac gene transcription.

Main Methods:

  • Investigated HRT protein interaction with GATA transcription factors.
  • Assessed HRT's effect on GATA-dependent transcription of cardiac gene promoters (e.g., ANF promoter).
  • Utilized adenovirus-mediated expression of Hrt2 in cultured cardiomyocytes and examined effects on cardiac-specific gene mRNA levels.
  • Explored the role of signaling molecules, such as Akt1, in modulating HRT-GATA interactions.

Main Results:

  • HRT proteins were found to inhibit GATA-dependent cardiac gene transcription.
  • HRT proteins physically interacted with GATA proteins, with the HRT basic domain being essential for this interaction and repression.
  • Adenovirus-mediated Hrt2 expression suppressed ANF and other cardiac-specific gene expression in cardiomyocytes.
  • Constitutively active Akt1 reversed Hrt2-mediated inhibition of GATA-dependent transcription.

Conclusions:

  • HRT proteins inhibit cardiac gene transcription by interfering with GATA transcription factors.
  • HRT proteins physically interact with GATA proteins, and this interaction is critical for transcriptional repression.
  • HRT proteins may regulate specific cardiac genes by modulating GATA protein function in a signal-dependent manner, influencing cardiac development and disease.

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