Two related coactivator complexes SAGA and ATAC control embryonic stem cell self-renewal through two different acetyltransferase-independent mechanisms; Fischer et al.; Western blot data

SAGA and ATAC are two related transcriptional coactivator complexes, sharing the same histone acetyltransferase (HAT) subunit. The HAT activities of SAGA and ATAC are required for metazoan development but the precise role of the two complexes in RNA polymerase II transcription in mammals is less understood. To determine whether SAGA and ATAC have redundant or specific functions dependent on their HAT activities, we compared the effects of HAT inactivation in each complex with that of inactivation of either SAGA or ATAC core subunits in mouse embryonic stem cells (ESCs). We show that core subunits of SAGA or ATAC subunits are required for complex assembly, mouse ESC growth and self-renewal. Additionally, ATAC, but not SAGA subunits are required for ESC viability by regulating the transcription of translation-related genes. Surprisingly, depletion of specific or shared HAT module subunits caused a global decrease in histone H3K9 acetylation, but did not result in significant phenotypic or transcriptional defects. Thus, our results indicate that SAGA and ATAC are differentially required for viability and self-renewal of mouse ESCs by regulating transcription through different pathways, in a HAT-independent manner.

SAGA与ATAC是两类结构相关的转录辅激活复合物，二者共享同一个组蛋白乙酰转移酶（histone acetyltransferase, HAT）亚基。SAGA和ATAC的HAT活性对于多细胞生物发育不可或缺，但二者在哺乳动物RNA聚合酶II（RNA polymerase II）转录过程中的具体功能仍未明确。为探究SAGA与ATAC的功能是存在冗余，还是依赖其HAT活性而具有特异性，我们在小鼠胚胎干细胞（ESCs）中，对比了失活各复合物HAT亚基与单独失活SAGA或ATAC核心亚基所产生的生物学效应。实验结果表明，SAGA或ATAC的核心亚基是复合物组装、小鼠ESC生长及自我更新所必需的。此外，ATAC（而非SAGA）亚基可通过调控翻译相关基因的转录，维持小鼠ESC的存活能力。令人意外的是，特异性或共享的HAT模块亚基的缺失会导致组蛋白H3K9乙酰化水平整体下降，但并未引发显著的表型或转录缺陷。综上，本研究结果显示，SAGA与ATAC可通过不同转录通路实现调控且不依赖HAT活性，二者在小鼠ESC的存活与自我更新过程中具有差异化的功能需求。