ID2蛋白在转录因子MESP1调控胚胎干细胞向心肌分化过程中的作用

Congenital heart diseases remain a leading cause of infant morbidity worldwide. Transcription factor MESP1, is an early regulator of cardiovascular differentiation in mammalian heart development. Owing to its transient expression nature during cardiac development and differentiation, the detailed mechanism of MESP1 remains unclear. As members of the Helix-Loop-Helix (HLH) protein superfamily, the transcription factor MESP1 and the negative transcriptional regulators IDs play vital roles in the development of the heart. In our preliminary work, IDs protein has been identified as the direct interacting partner of MESP1 and affected the differentiation of human embryonic stem cells into cardiomyocytes. Thus we hypothesize that IDs are involved in regulating the binding affinity of MESP1 with its target genes by the formation of heterodimer. And the heterodimer contributes to the specific differentiation of MESP1-positive progenitors to cardiovascular cells. This study will provide reliable testimony and possibly a new target gene for the early diagnosis of congenital heart disease.

心脏发育异常是妊娠胚胎停止发育的重要原因，而其内在机制尚不清晰。申请人关注于心脏发育分化早期的转录因子MESP1，因其在胚胎发育中非常短暂的表达特性，MESP1调控心血管祖细胞分化的具体机制仍未阐明。蛋白MESP1和ID2同为Helix-Loop-Helix (HLH)蛋白超家族成员，都与心脏发育密切相关。ID2蛋白可作为HLH蛋白的负向调控因子。通过酵母双杂交实验，我们首次发现了二者间直接的相互作用；Co-IP实验进一步证实了二者结合形成异源二聚体。但其相互作用对下游靶基因的调控，特别是对心肌细胞分化成熟的调节机制尚不清楚，因此我们拟明确二者相互结合的位点，所形成的异源二聚体对MESP1启动下游靶基因转录的影响，并深入探讨MESP1是否通过招募负性调控因子ID2进而特异性调节向心血管的分化。这一研究将进一步完善心脏发育成熟的机制，也为产前诊断先天性心脏发育异常提供新的基因筛选靶点。