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Congenital Heart Defects with GATA Transcription Factors

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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  1. Congenital Heart Defects with GATA Transcription Factors By: Ben Devenney Biochemistry 2007

  2. 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

  3. 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)

  4. CHD Testing • Physical Appearance • X-Ray • Electrocardiogram • Echocardiogram • Palpation • Arterial Pulse

  5. 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.

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

  7. Heart Development

  8. 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.

  9. 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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