Sex-dependent gene regulatory networks of the heart rhythm

ABSTRACT: Expression level, control and intercoordination of 66 selected heart rhythm determinant (HRD) genes were compared in atria and ventricles of 4 male and 4 female adult mice. We found that genes encoding various adrenergic receptors, ankyrins, ion channels and transporters, connexins and other components of the intercalated discs form a complex network that is chamber dependent and differs between the two sexes. In addition, most HRD genes in atria had higher expression in males than in females, while in ventricles expression levels were mostly higher in females than in males. Moreover, significant chamber-differences were observed between the sexes, with higher expression in atria than ventricles for males and higher expression in ventricles than atria for females. We have ranked the selected genes according to their prominence in controlling the HRD gene web through expression coordination with the other web genes and protecting the web though their own expression stability. Interestingly, the prominence hierarchy was substantially different between the two sexes. Taken together these findings indicate that the organizational principles of the heart rhythm transcriptome are sex-dependent, with the newly introduced prominence analysis allowing identification of genes that are pivotal for the sexual dichotomy.

ORGANISM(S): Mus musculus

PROVIDER: GSE17324 | GEO | 2009/08/12

SECONDARY ACCESSION(S): PRJNA119003

REPOSITORIES: GEO