Gene expression data of postnatal Pitx2 deficient heart

Pitx2 is the homeobox gene located in proximity to the human 4q25 familial atrial fibrillation locus. Pitx2 haploinsufficient mice are prone to pacing induced atrial fibrillation indicating that reduced Pitx2 promotes an arrhythmogenic substrate within the atrium. Here, we inactivated Pitx2 in postnatal heart and discovered that unstressed adult Pitx2 mutant mice had sinus node dysfunction with impaired atrial conduction, an arrhythmia closely associated with atrial fibrillation. A genome-wide search for Pitx2 transcriptional targets using ChIP-sequencing and RNA expression profiling shows that Pitx2 represses target genes encoding cell junction proteins, ion channels, and critical transcriptional regulators many of which have been implicated in human atrial fibrillation by genome wide association studies. Pitx2 control and mutant hearts were collected from 3-, 6- and 12-week-old mice. At each time point, three controls and three mutants were collected as biological replicates. cDNA microarray analysis was performed using Affymetrix GeneChip Mouse Genome 430 2.0 Array (Affymetrix, Santa Clara, CA).Pitx2是定位于人类4q25家族性心房颤动位点附近的同源盒基因。Pitx2单倍剂量不足小鼠易发生起搏诱导性心房颤动，这表明Pitx2表达降低会促进心房内致心律失常底物的形成。本研究中，我们在小鼠出生后心脏中灭活Pitx2基因，发现无应激状态下的成年Pitx2突变小鼠存在窦房结功能障碍伴心房传导受损，这类心律失常与心房颤动密切相关。本研究通过染色质免疫共沉淀测序（ChIP-sequencing）与RNA表达谱分析，对Pitx2的转录靶基因开展全基因组筛选，结果显示Pitx2可抑制编码细胞连接蛋白、离子通道及关键转录调控因子的靶基因，其中众多靶基因已通过全基因组关联研究被证实与人类心房颤动相关。我们分别从3周、6周及12周龄的小鼠体内采集Pitx2野生型与突变型心脏样本，每个时间点均采集3份野生型样本与3份突变型样本作为生物学重复。实验采用Affymetrix GeneChip小鼠基因组430 2.0芯片（Affymetrix，美国加利福尼亚州圣克拉拉市）完成cDNA微阵列分析。