Program in Molecular Carcinogenesis, Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Science Park, Smithville, TX 78957, USA.
Epigenomics. 2014 Jun;6(3):329-39. doi: 10.2217/epi.14.22.
Precise regulation of gene expression programs during embryo development requires cooperation between transcriptional factors and histone-modifying enzymes, such as the Gcn5 histone acetyltransferase. Gcn5 functions within a multi-subunit complex, called SAGA, that is recruited to specific genes through interactions with sequence-specific DNA-binding proteins to aid in gene activation. Although the transcriptional programs regulated by SAGA in embryos are not well defined, deletion of either Gcn5 or USP22, the catalytic subunit of a deubiquitinase module in SAGA, leads to early embryonic lethality. Here, we review the known functions of Gcn5, USP22 and associated proteins during development and discuss how these functions might be related to human disease states, including cancer and neurodegenerative diseases.
胚胎发育过程中基因表达程序的精确调控需要转录因子和组蛋白修饰酶(如 Gcn5 组蛋白乙酰转移酶)之间的合作。Gcn5 作为一个多亚基复合物(称为 SAGA)的一部分发挥作用,该复合物通过与特定 DNA 结合蛋白的相互作用被募集到特定基因上,以帮助基因激活。尽管 SAGA 在胚胎中调控的转录程序尚未得到很好的定义,但 Gcn5 或 SAGA 中去泛素化酶模块的催化亚基 USP22 的缺失都会导致早期胚胎致死。在这里,我们回顾了 Gcn5、USP22 及其相关蛋白在发育过程中的已知功能,并讨论了这些功能如何与人类疾病状态(包括癌症和神经退行性疾病)相关。