Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX, USA.
The Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Epigenetics Chromatin. 2021 Jun 10;14(1):26. doi: 10.1186/s13072-021-00402-x.
The SAGA complex is an evolutionarily conserved transcriptional coactivator that regulates gene expression through its histone acetyltransferase and deubiquitylase activities, recognition of specific histone modifications, and interactions with transcription factors. Multiple lines of evidence indicate the existence of distinct variants of SAGA among organisms as well as within a species, permitting diverse functions to dynamically regulate cellular pathways. Our co-expression analysis of genes encoding human SAGA components showed enrichment in reproductive organs, brain tissues and the skeletal muscle, which corresponds to their established roles in developmental programs, emerging roles in neurodegenerative diseases, and understudied functions in specific cell types. SAGA subunits modulate growth, development and response to various stresses from yeast to plants and metazoans. In metazoans, SAGA further participates in the regulation of differentiation and maturation of both innate and adaptive immune cells, and is associated with initiation and progression of diseases including a broad range of cancers. The evolutionary conservation of SAGA highlights its indispensable role in eukaryotic life, thus deciphering the mechanisms of action of SAGA is key to understanding fundamental biological processes throughout evolution. To illuminate the diversity and conservation of this essential complex, here we discuss variations in composition, essentiality and co-expression of component genes, and its prominent functions across Fungi, Plantae and Animalia kingdoms.
SAGA 复合物是一种进化上保守的转录共激活因子，通过其组蛋白乙酰转移酶和去泛素化酶活性、识别特定的组蛋白修饰、以及与转录因子的相互作用来调节基因表达。多条证据表明，SAGA 在不同生物体内以及同一物种内存在不同的变体，从而能够动态调节细胞通路的多种功能。我们对编码人类 SAGA 成分的基因进行共表达分析表明，这些基因在生殖器官、脑组织和骨骼肌中富集，这与它们在发育程序中的既定作用、在神经退行性疾病中的新兴作用以及在特定细胞类型中研究不足的功能相对应。SAGA 亚基调节从酵母到植物和后生动物的生长、发育和对各种应激的反应。在后生动物中，SAGA 进一步参与先天和适应性免疫细胞的分化和成熟的调节，并与包括广泛的癌症在内的多种疾病的起始和进展有关。SAGA 的进化保守性突出了它在真核生物生命中的不可或缺的作用，因此，破译 SAGA 的作用机制是理解整个进化过程中基本生物学过程的关键。为了阐明这个基本复合物的多样性和保守性，我们在这里讨论了组成、必需性和成分基因共表达的变化，以及它在真菌、植物和动物王国中的突出功能。
