Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510100, China.
The Center for Heart Development, State Key Lab of Development Biology of Freshwater Fish, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410000, China.
Biochem Soc Trans. 2020 Aug 28;48(4):1781-1794. doi: 10.1042/BST20200393.
Pygo is a nuclear protein containing two conserved domains, NHD and PHD, which play important roles in embryonic development and carcinogenesis. Pygo was first identified as a core component of the Wnt/β-catenin signalling pathway. However, it has also been reported that the function of Pygo is not always Wnt/β-catenin signalling dependent. In this review, we summarise the functions of both domains of Pygo and show that their functions are synergetic. The PHD domain mainly combines with transcription co-factors, including histone 3 and Bcl9/9l. The NHD domain mainly recruits histone methyltransferase/acetyltransferase (HMT/HAT) to modify lysine 4 of the histone 3 tail (H3K4) and interacts with Chip/LIM-domain DNA-binding proteins (ChiLS) to form enhanceosomes to regulate transcriptional activity. Furthermore, we summarised chromatin modification differences of Pygo in Drosophila (dPygo) and vertebrates, and found that Pygo displayes a chromatin silencing function in Drosophila, while in vertebates, Pygo has a chromatin-activating function due to the two substitution of two amino acid residues. Next, we confirmed the relationship between Pygo and Bcl9/9l and found that Pygo-Bcl/9l are specifically partnered both in the nucleus and in the cytoplasm. Finally, we discuss whether transcriptional activity of Pygo is Wnt/β-catenin dependent during embryonic development. Available information indications that the transcriptional activity of Pygo in embryonic development is either Wnt/β-catenin dependent or independent in both tissue-specific and cell-specific-modes.
Pygo 是一种含有两个保守结构域的核蛋白，NHD 和 PHD，它们在胚胎发育和致癌作用中发挥重要作用。Pygo 最初被鉴定为 Wnt/β-catenin 信号通路的核心组成部分。然而，也有报道称 Pygo 的功能并不总是依赖于 Wnt/β-catenin 信号。在这篇综述中，我们总结了 Pygo 两个结构域的功能，并表明它们的功能是协同的。PHD 结构域主要与转录共因子结合，包括组蛋白 3 和 Bcl9/9l。NHD 结构域主要招募组蛋白甲基转移酶/乙酰转移酶（HMT/HAT）来修饰组蛋白 3 尾的赖氨酸 4（H3K4），并与 Chip/LIM 结构域 DNA 结合蛋白（ChiLS）相互作用形成增强子来调节转录活性。此外，我们总结了果蝇（dPygo）和脊椎动物中 Pygo 的染色质修饰差异，发现 Pygo 在果蝇中表现出染色质沉默功能，而在脊椎动物中，由于两个氨基酸残基的替换，Pygo 具有染色质激活功能。接下来，我们证实了 Pygo 与 Bcl9/9l 的关系，并发现 Pygo-Bcl/9l 特异性地在核内和细胞质中结合。最后，我们讨论了 Pygo 在胚胎发育过程中的转录活性是否依赖于 Wnt/β-catenin。现有信息表明，Pygo 在胚胎发育过程中的转录活性在组织特异性和细胞特异性模式下均依赖或不依赖于 Wnt/β-catenin。
