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Cx30.2 enhancer analysis identifies Gata4 as a novel regulator of atrioventricular delay

By Nikhil V. Munshi, John McAnally, Svetlana Bezprozvannaya, Jeff M. Berry, James A. Richardson, Joseph A. Hill and Eric N. Olson

Abstract

The cardiac conduction system comprises a specialized tract of electrically coupled cardiomyocytes responsible for impulse propagation through the heart. Abnormalities in cardiac conduction are responsible for numerous forms of cardiac arrhythmias, but relatively little is known about the gene regulatory mechanisms that control the formation of the conduction system. We demonstrate that a distal enhancer for the connexin 30.2 (Cx30.2, also known as Gjd3) gene, which encodes a gap junction protein required for normal atrioventricular (AV) delay in mice, is necessary and sufficient to direct expression to the developing AV conduction system (AVCS). Moreover, we show that this enhancer requires Tbx5 and Gata4 for proper expression in the conduction system, and Gata4+/- mice have short PR intervals indicative of accelerated AV conduction. Thus, our results implicate Gata4 in conduction system function and provide a clearer understanding of the transcriptional pathways that impact normal AV delay

Topics: Development and Disease
Publisher: Company of Biologists
OAI identifier: oai:pubmedcentral.nih.gov:2709072
Provided by: PubMed Central
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