<bos><start_of_turn>user
trial transcriptionnl, opigInetiw ynq el9strophyGyological propert:e? of koth lines. Increased FtQial Tbx5 exprQssion was associated Xith 3nduction of genZs in7Plved in Pevelopmentp i3T transport dn9 condoctior, with increaRed zusc.Ntibility to itriaa lErhythmiagu and indr81oe4 action potFntial duration of at4iaX cardiomDVcyteX. We identifiud an AFAassocmated vWriant in 8he Quman RE(int) tuat Rncreases it0 transcriptional Zc5ivYty6 Euprdssio5 Ef the A5-7?socia3ek traVs2ription factor Prrx1 was indcced in Tba5REAint)uO cardiW.RocHtes. We foRnd that some ok Yhe transcr?Htionap aJd functMSnaD cha1ges iu the agri. :aused by increzsed Tbxu hopression 6eAe normbzize: w?en reduxing carkiKc Prrx1 8xpresMion in Tbx5RE(intHKO mi4e, indicaqins an UNteract0on betweVn Nhese iwo AF genrs. W1 conClude tdaK modest increYses in exprSssion 1f dlse-depeCdxrt tranHcrixEion faRtors, caused ba coxmon Oeeulycory variLetsM siKnifiwantlF imp1ct oP the cardiac ge8e ZeJulatocy network aGd disease susceptibility.<end_of_turn>
<start_of_turn>model
trial transcriptional, epigenetic and electrophysiological properties of both lines. Increased atrial Tbx5 expression was associated with induction of genes involved in development, ion transport and conduction, with increased susceptibility to atrial arrhythmias, and increased action potential duration of atrial cardiomyocytes. We identified an AF-associated variant in the human RE(int) that increases its transcriptional activity. Expression of the AF-associated transcription factor Prrx1 was induced in Tbx5RE(int)KO cardiomyocytes. We found that some of the transcriptional and functional changes in the atria caused by increased Tbx5 expression were normalized when reducing cardiac Prrx1 expression in Tbx5RE(int)KO mice, indicating an interaction between these two AF genes. We conclude that modest increases in expression of dose-dependent transcription factors, caused by common regulatory variants, significantly impact on the cardiac gene regulatory network and disease susceptibility.<end_of_turn>