Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Arrheniuslaboratories E3, SE-106 91 Stockholm, Sweden.
Exp Cell Res. 2014 Feb 1;321(1):47-57. doi: 10.1016/j.yexcr.2013.10.010. Epub 2013 Oct 22.
A combination of broadly expressed transcriptional activators and spatially restricted repressors are used to pattern embryos into cells of different fate. Transcriptional co-regulators are essential mediators of transcription factor function, and contribute to selective transcriptional responses in embryo development. A two step mechanism of transcriptional regulation is discussed, where remodeling of chromatin is initially required, followed by stimulation of recruitment or release of RNA polymerase from the promoter. Transcriptional co-regulators are essential for both of these steps. In particular, most co-activators are associated with histone acetylation and co-repressors with histone deacetylation. In the early Drosophila embryo, genome-wide studies have shown that the CBP co-activator has a preference for associating with some transcription factors and regulatory regions. The Groucho, CtBP, Ebi, Atrophin and Brakeless co-repressors are selectively used to limit zygotic gene expression. New findings are summarized which show that different co-repressors are often utilized by a single repressor, that the context in which a co-repressor is recruited to DNA can affect its activity, and that co-regulators may switch from co-repressors to co-activators and vice versa. The possibility that co-regulator activity is regulated and plays an instructive role in development is discussed as well. This review highlights how findings in Drosophila embryos have contributed to the understanding of transcriptional regulation in eukaryotes as well as to mechanisms of animal embryo patterning.
广泛表达的转录激活因子和空间限制的抑制因子的组合用于将胚胎模式化为具有不同命运的细胞。转录共调节因子是转录因子功能的重要介质,并有助于胚胎发育中的选择性转录反应。讨论了转录调控的两步机制,其中最初需要重塑染色质,然后刺激 RNA 聚合酶从启动子募集或释放。转录共调节因子对于这两个步骤都是必不可少的。特别是,大多数共激活因子与组蛋白乙酰化相关,而共抑制因子与组蛋白去乙酰化相关。在早期果蝇胚胎中,全基因组研究表明,CBP 共激活因子与一些转录因子和调控区域具有优先结合的倾向。Groucho、CtBP、Ebi、Atrophin 和 Brakeless 共抑制因子被选择性地用于限制合子基因表达。总结了新的发现,这些发现表明,单个抑制因子通常利用不同的共抑制因子,共抑制因子在 DNA 上募集的上下文可以影响其活性,并且共调节因子可以从共抑制因子转变为共激活因子,反之亦然。还讨论了共调节因子活性受到调节并在发育中发挥指导作用的可能性。这篇综述强调了果蝇胚胎中的发现如何有助于理解真核生物中的转录调控以及动物胚胎模式形成的机制。