Robust coordination of cardiac functions from gene co-expression reveals a versatile combinatorial transcriptional control.

ABSTRACT

The necessary overall coordination of cardiac cellular functions is little known at the mRNA level. Focusing on energy production and cardiac contraction, we analyzed microarray data from heart tissue obtained in groups of mice and rats in normal conditions and with a left ventricular dysfunction. In each group and for each function, we identified genes positively or negatively correlated with numerous genes of the function, which were called coordinated or inversely coordinated with the function. The genes coordinated with energy production or cardiac contraction showed the coupling of these functions in all groups. Among coordinated or inversely coordinated genes common to the two functions, we proposed a fair number of transcriptional regulators as potential determinants of the energy production and cardiac contraction coupling. Although this coupling was constant across the groups and unveiled a stable gene core, the combinations of transcriptional regulators were very different between the groups, including one half that has never been linked to heart function. These results highlighted the stable coordination of energy production or cardiac contraction at the mRNA level, and the combinatorial and versatile nature of potential transcriptional regulation. In addition, this work unveiled new transcriptional regulators potentially involved in normal or altered cardiac functional coupling.