Variation in a Left Ventricle-Specific Hand1 Enhancer Impairs GATA Transcription Factor Binding and Disrupts Conduction System Development and Function.

ABSTRACT:

Rationale

The ventricular conduction system (VCS) rapidly propagates electrical impulses through the working myocardium of the ventricles to coordinate chamber contraction. GWAS (Genome-wide association studies) have associated nucleotide polymorphisms, most are located within regulatory intergenic or intronic sequences, with variation in VCS function. Two highly correlated polymorphisms (r²>0.99) associated with VCS functional variation (rs13165478 and rs13185595) occur 5' to the gene encoding the basic helix-loop-helix transcription factor HAND1 (heart- and neural crest derivatives-expressed protein 1).

Objective

Here, we test the hypothesis that these polymorphisms influence HAND1 transcription thereby influencing VCS development and function.

Methods and re

SUBMITTER: Vincentz JW 

PROVIDER: S-EPMC6715539 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature