GATA Co-Factors : Collaborators in Cardiac Development, Conspirators in Cardiac Disease
Disruption of fetal gene expression during cardiac development can result in congenital heart defects (CHDs), the most common developmental anomaly in humans and the leading non-infectious cause of death in newborns. The reactivation of fetal gene expression during cardiac hypertrophy in the adult is an adaptive response to pressure or volume overloads, but can lead to impaired cardiac function. Gata4, a member of a family of zinc-finger transcription factors, has been implicated as a key regulator of fetal cardiac gene expression during cardiac development and cardiac hypertrophy. This thesis work presents two novel transcriptional complexes likely found in these settings, one that cooperates to activate GATA-dependent transactivation and one that represses it.