Torok Michael S, Pray-Grant Marilyn G, Grant Benjamin M, Josephs Meagan E, Grant Patrick A
Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
J Mol Genet (Isleworth). 2019 Nov;2(1). Epub 2019 Jun 10.
The post-translational acetylation of the histone components of chromatin mediates numerous DNA-templated events, including transcriptional activation, DNA repair, and genomic replication. The conserved SAGA (Spt-Ada-Gcn5 Acetyltranferase) and SLIK (SAGA-Like) Histone Acetyltransferase (HAT) complexes are required for transcriptional activation of a subset of yeast genes and contain multiple subunits including the histone fold-containing TBP- Associated Factors (TAFs): 6, 9, 10, and 12. These TAFs are also components of the TFIID complex and are consequently involved in most RNA polymerase II-transcription in yeast. Here we identify a novel conserved region of TAF12, termed ReNu, outside of its histone fold, which is required for SAGA and SLIK-directed nucleosomal acetylation. We demonstrate that this region is not required for chromatin association, but show that this region plays an important role for histone H3 acetylation at specific SAGA and SLIK-regulated promoters. Our data suggests that the ReNu region of TAF12 regulates Gcn5 acetylation of specific substrates within the SAGA super-family of HAT complexes.
染色质组蛋白成分的翻译后乙酰化介导了众多以DNA为模板的事件，包括转录激活、DNA修复和基因组复制。保守的SAGA（Spt-Ada-Gcn5乙酰转移酶）和SLIK（类SAGA）组蛋白乙酰转移酶（HAT）复合物是酵母部分基因转录激活所必需的，且包含多个亚基，其中包括含组蛋白折叠的TBP相关因子（TAF）：6、9、10和12。这些TAF也是TFIID复合物的组成部分，因此参与酵母中大多数RNA聚合酶II介导的转录过程。在此，我们在TAF12的组蛋白折叠结构域外鉴定出一个名为ReNu的新型保守区域，它是SAGA和SLIK介导的核小体乙酰化所必需的。我们证明该区域对于染色质结合并非必需，但表明该区域在特定SAGA和SLIK调控的启动子处的组蛋白H3乙酰化过程中发挥重要作用。我们的数据表明，TAF12的ReNu区域在HAT复合物的SAGA超家族中调节特定底物的Gcn5乙酰化。
