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p53 regulates the cardiac transcriptome.

Tak W Mak1, Ludger Hauck2, Daniela Grothe2

  • 1Campbell Family Cancer Research Institute, Princess Margaret Hospital, Toronto, ON, Canada M5G 2M9; phyllis.billia@uhn.ca tmak@uhnres.utoronto.ca.

Proceedings of the National Academy of Sciences of the United States of America
|February 15, 2017
PubMed
Summary
This summary is machine-generated.

The tumor suppressor Trp53 (p53) is a master regulator of the heart

Keywords:
cardiac hypertrophycardiomyopathyheart failuretranscriptometumor suppressor

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Area of Science:

  • Cardiovascular Biology
  • Molecular Biology
  • Gene Regulation

Background:

  • The tumor suppressor Trp53 (p53) is known to inhibit cell growth after acute stress.
  • Its role in regulating cardiac tissue homeostasis under normal physiological conditions is not well understood.

Purpose of the Study:

  • To investigate the physiological role of p53 in adult cardiomyocytes in vivo.
  • To identify p53-regulated genes and pathways in the adult heart.

Main Methods:

  • Conditional gene targeting using Cre-loxP system in adult mice.
  • Genome-wide transcriptome analyses (RNA sequencing) of heart-specific p53 knockout mice.
  • Genome-wide annotation and pathway analyses of differentially expressed transcripts.

Main Results:

  • Over 5,000 differentially expressed transcripts were identified, forming p53-regulated gene clusters.
  • >20 gene sets, including over 1,000 genes, were found relevant to cardiac architecture and function.
  • p53 regulates cardiac architecture, excitation-contraction coupling, mitochondrial biogenesis, and oxidative phosphorylation.
  • p53 deficiency confers resistance to acute biomechanical stress in the heart.

Conclusions:

  • p53 is a previously unrecognized master regulator of the cardiac transcriptome under physiological conditions.
  • p53 plays a complex role in maintaining cardiac homeostasis and function.