Cardiovascular Genetics, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Adv Exp Med Biol. 2024;1441:295-311. doi: 10.1007/978-3-031-44087-8_16.
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.
心脏发育是一个由复杂转录网络调控的精细过程,其中转录因子(TFs)与其他调控层相互作用。在本章中,我们介绍了核心心脏 TFs,包括 Gata、Hand、Nkx2、Mef2、Srf 和 Tbx。这些因子相互调节彼此的表达,并且可以在下游靶标上以组合方式发挥作用。它们的缺失会导致小鼠出现各种心脏表型,而人类的突变与先天性心脏病有关。在本章的第二部分,我们讨论了不同层次的调控,包括顺式调控元件、染色质结构和 microRNAs,它们可以与转录因子相互作用,调节其功能,或者是下游靶标。最后,提供了导致人类先天性心脏病的心脏调控网络紊乱的例子。