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目的转录因子MEF2通过调控肌肉特异表达基因在病理性心肌肥厚的发生发展中发挥重要的作用,但是直到目前,MEF2下游靶基因所知甚少。方法和结果我们使用自主研发的cardiosignalscan对人、小鼠和原鸡的全基因组核心启动子序列进行筛选,发现了111条启动子区含有MEF2保守结合位点的基因。整合EST表达序列数据库后,我们发现C3orf43和C10orf71是两条受MEF2调控同时在肌肉特异表达的新基因。进一步的功能研究表明,C10orf71在病理性心脏肥厚中显著升高1.6倍(P=0.012),提示C10orf71可能参与了病理性心肌肥厚病程。结论 C10orf71是一个新的受MEF2调控的在肌肉特异表达的新基因,并可能参与了病理性心肌肥厚病程。
The transcription factor MEF2 plays an important role in the development of pathological myocardial hypertrophy through the regulation of muscle-specific gene expression, but until now, the MEF2 downstream target genes are poorly understood. METHODS AND RESULTS We sequenced the genome-wide core promoter sequences of human, mouse and chicken using our self-developed cardiosignalscan and found 111 promoter regions containing MEF2 conserved binding sites. After integration of the EST expression sequence database, we found that C3orf43 and C10orf71 are two new genes that are regulated by MEF2 and are also specifically expressed in muscle. Further functional studies showed that C10orf71 was significantly increased by 1.6-fold in pathologic cardiac hypertrophy (P = 0.012), suggesting that C10orf71 may be involved in the pathological course of cardiac hypertrophy. Conclusion C10orf71 is a new MEF2-specific gene that is specifically expressed in muscle and may be involved in the pathogenesis of pathological myocardial hypertrophy.