心脏发育是一个由复杂的转录网络控制的微调过程,其中转录因子(TF)与其他调节层相互作用。在这一章中,我们介绍核心心脏TFs,包括Gata,手,Nkx2,Mef2,Srf,Tbx这些因子调节彼此的表达,并且还可以组合方式作用于它们的下游靶标。它们的破坏导致小鼠的各种心脏表型,人类的突变与先天性心脏缺陷有关。在本章的第二部分,我们讨论了不同级别的监管,包括顺式监管元素,染色质结构,和microRNAs,可以与转录因子相互作用,调节它们的功能,或者是下游目标。最后,提供了导致人类先天性心脏病的心脏调节网络紊乱的例子。
Cardiac development is a fine-tuned process governed by complex transcriptional networks, in which transcription factors (TFs) interact with other regulatory layers. In this chapter, we introduce the core cardiac TFs including Gata, Hand, Nkx2, Mef2, Srf, and Tbx. These factors regulate each other\'s expression and can also act in a combinatorial manner on their downstream targets. Their disruption leads to various cardiac phenotypes in mice, and mutations in humans have been associated with congenital heart defects. In the second part of the chapter, we discuss different levels of regulation including cis-regulatory elements, chromatin structure, and microRNAs, which can interact with transcription factors, modulate their function, or are downstream targets. Finally, examples of disturbances of the cardiac regulatory network leading to congenital heart diseases in human are provided.