Bhattacharyya et al (J Clin Invest 2023;133:e153635, PMID 36454649) globally profiled the mouse cardiac conduction system (CCS) cis-regulatory landscape by genetically tagged CCS component-specific nuclei for comprehensive assay for transposase-accessible chromatin-sequencing (ATAC-Seq) analysis. A global CCS-enriched cis-regulatory element (CRE) database, referred to as CCS-ATAC, was established as a key resource for studying CCS-wide and component-specific regulatory functions. Using transcription factor (TF) motifs to construct CCS component-specific gene regulatory networks, the authors identified and independently confirmed several specific TF subnetworks. Furthermore, CCS-ATAC was used to improve the annotation of existing human variants related to cardiac rhythm and nominated a potential enhancer-target pair that was dysregulated by a specific single nucleotide polymorphism. The authors conclude that the established CCS-regulatory compendium identified novel CCS enhancer elements and illuminated potential functional associations between human genomic variants and CCS component-specific CREs.
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Published online: February 08, 2023
Publication stageIn Press Journal Pre-Proof
Funding Sources: The author has no funding sources to disclose. Disclosures: The author has no conflicts of interest to disclose.
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