Abstract
The current study by Bosada et al (Circ Res 2021. https://doi.org/10.1161/CIRCRESAHA.121.319146; PMID: 34092116) investigated the effects of a genetic variant region at 1q24, found to be highly associated with atrial fibrillation (AF), close to PRRX1, encoding the paired related homeobox 1 transcription factor. Deletion of the mouse orthologue of the noncoding variant genomic region (R1A) at 1q24 resulted in the downregulation of Prrx1 gene expression in cardiomyocytes. In addition, a cardiomyocyte lineage–specific gene program (Mhrt, Myh6, Rbm20, Tnnt2, Ttn, Ckm) was upregulated in R1A-/- atrial cardiomyocytes, and Mef2 binding motifs were significantly enriched at differentially accessible chromatin sites.
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