Congenital heart defects with gata transcription factors
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Congenital Heart Defects with GATA Transcription Factors. By: Ben Devenney Biochemistry 2007. Basic Facts. Congenital Heart Defects occurs in 5-8 out of every 1000 births- most common major birth defect 85% of those survive into adulthood

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Congenital Heart Defects with GATA Transcription Factors

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Congenital Heart Defects with GATA Transcription Factors

By: Ben Devenney

Biochemistry 2007


Basic Facts

  • Congenital Heart Defects occurs in 5-8 out of every 1000 births- most common major birth defect

  • 85% of those survive into adulthood

  • Approx 1 million adults in world today born with some sort of CHD.

  • Heart is first organ to form in body.

  • Primarily Genetic


Various Forms of CHD

  • Heart Murmur

  • Atrial Septal Defect

  • Coarctation of the Aorta

  • Ventricular Septal Defect

  • Aortic Stenosis

  • Cardiac Malpositions (ex- heart on right side)


CHD Testing

  • Physical Appearance

  • X-Ray

  • Electrocardiogram

  • Echocardiogram

  • Palpation

  • Arterial Pulse


Causes of CHD

  • Scientists still learning about heart formation and specific causes through Gene Targeting Experiments

  • Occurs in error of instructions given to the developmental cells.

  • GATA Family largely responsible for heart formation.


Animals used for Gene Targeting Experiments in studying the Human Heart.


Heart Development


GATA Transcription Factors

  • 6 GATA factors, but GATA -4 is primary one found to cause heart defects.

  • GATA-4 regulates the second stage of cardiac development.

  • GATA proteins are part of zinc finger transcription factor.

  • Zinc Finger: a finger-shaped fold in a protein that permits it to interact with DNA and RNA. The fold is created by the binding of specific amino acids in the protein to a zinc atom.


GATA-4

  • Found on Chromosome 8p23.1-p22

  • Impairs ventricular growth

  • Necessary for sequence specific DNA binding activity

  • Procardiomyocytes fail to migrate from anterior to dorsal region of the embryo to ventral midline to form linear heart tube.

  • “Forced expression on GATA-4 in P19 cells accelerate cardiogenesis and increased the number of cardiac myocytes”

  • On N-terminus of GATA-4, transcriptional activation domains identified (ADI and ADII)

  • Both AD’s contain Tyrosine and Serine residues meaning posttranslational modifications of GATA-4


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