The related coactivator complexes SAGA and ATAC control embryonic stem cell self-renewal through acetyltransferase-independent mechanisms.

The related coactivator complexes SAGA and ATAC control embryonic stem cell self-renewal through acetyltransferase-independent mechanisms.
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DOI:
10.1016/j.celrep.2021.109598
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发表时间:
2021-08-24
期刊:
影响因子:
8.8
通讯作者:
Devys D
Devys D
中科院分区:
生物学1区
文献类型:
--
作者:
Fischer V;Plassard D;Ye T;Reina-San-Martin B;Stierle M;Tora L;Devys D

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佐贺(Spt-Ada-Gcn 5 acetyltransferase)和ATAC(Ada-two-A-containing)是两种相关的共激活因子复合物,具有相同的组蛋白乙酰转移酶(HAT)亚基。多细胞动物的发育需要佐贺和ATAC的HAT活性,但这些复合物在RNA聚合酶II转录中的作用尚不清楚。为了确定佐贺和ATAC是否具有冗余或特定的功能,我们将每个复合物中的HAT失活的影响与小鼠胚胎干细胞(ESC)中佐贺或ATAC核心亚基的失活进行比较。我们发现,佐贺或ATAC的核心亚基是复杂的组装和小鼠ESC的生长和自我更新所必需的。令人惊讶的是,HAT模块亚基的缺失导致组蛋白H3 K9乙酰化的整体降低,但不会导致显著的表型或转录缺陷。因此,我们的研究结果表明,佐贺和ATAC的差异需要通过调节转录通过不同的途径在一个HAT独立的方式自我更新的小鼠胚胎干细胞。Fischer等人分析了佐贺和ATAC共激活因子复合物在小鼠胚胎干细胞(ESC)中共享组蛋白乙酰转移酶(HAT)亚基的作用。作者将这些复合物的核心和HAT活性分开,以表明它们通过HAT独立途径在维持ESC中发挥非冗余作用。
SAGA (Spt-Ada-Gcn5 acetyltransferase) and ATAC (Ada-two-A-containing) are two related coactivator complexes, sharing the same histone acetyltransferase (HAT) subunit. The HAT activities of SAGA and ATAC are required for metazoan development, but the role of these complexes in RNA polymerase II transcription is less understood. To determine whether SAGA and ATAC have redundant or specific functions, we compare 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 are required for complex assembly and mouse ESC growth and self-renewal. Surprisingly, depletion of HAT module subunits causes a global decrease in histone H3K9 acetylation, but does not result in significant phenotypic or transcriptional defects. Thus, our results indicate that SAGA and ATAC are differentially required for self-renewal of mouse ESCs by regulating transcription through different pathways in a HAT-independent manner. Fischer et al. analyze the role of SAGA and ATAC coactivator complexes that share a histone acetyltransferase (HAT) subunit in mouse embryonic stem cells (ESCs). The authors separate the core and HAT activities of these complexes to show that they play non-redundant roles in maintaining ESCs, through HAT-independent pathways.
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