Department of Functional Genomics, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR 7104, INSERM U 964, Université de Strasbourg, BP 10142, 67404 Illkirch Cedex, CU de Strasbourg, France.
Cell Mol Life Sci. 2010 Feb;67(4):611-28. doi: 10.1007/s00018-009-0199-8. Epub 2009 Nov 21.
Histone acetyl transferases (HATs) play a crucial role in eukaryotes by regulating chromatin architecture and locus-specific transcription. The GCN5 HAT was identified as a subunit of the SAGA (Spt-Ada-Gcn5-Acetyltransferase) multiprotein complex. Vertebrate cells express a second HAT, PCAF, that is 73% identical to GCN5. Here, we report the characterization of the mammalian ATAC (Ada-Two-A-Containing) complexes containing either GCN5 or PCAF in a mutually exclusive manner. In vitro ATAC complexes acetylate lysine 14 of histone H3. Moreover, ATAC- or SAGA-specific knock-down experiments suggest that both ATAC and SAGA are involved in the acetylation of histone H3K9 and K14 residues. Despite their catalytic similarities, SAGA and ATAC execute their coactivator functions on distinct sets of inducible target genes. Interestingly, ATAC strongly influences the global phosphorylation level of histone H3S10, suggesting that in mammalian cells a cross-talk exists linking ATAC function to H3S10 phosphorylation.
组蛋白乙酰转移酶 (HATs) 在真核生物中通过调节染色质结构和特定基因座的转录发挥着关键作用。GCN5 HAT 被鉴定为 SAGA（Spt-Ada-Gcn5-Acetyltransferase）多蛋白复合物的一个亚基。脊椎动物细胞表达第二种 HAT，即 PCAF，它与 GCN5 有 73%的同源性。在这里，我们报告了以相互排斥的方式含有 GCN5 或 PCAF 的哺乳动物 ATAC（Ada-Two-A-Containing）复合物的特性。体外 ATAC 复合物乙酰化组蛋白 H3 的赖氨酸 14。此外，ATAC 或 SAGA 特异性敲低实验表明，ATAC 和 SAGA 都参与组蛋白 H3K9 和 K14 残基的乙酰化。尽管它们的催化相似，但 SAGA 和 ATAC 在不同的诱导靶基因上执行其共激活因子功能。有趣的是，ATAC 强烈影响组蛋白 H3S10 的全局磷酸化水平，这表明在哺乳动物细胞中，存在一种将 ATAC 功能与 H3S10 磷酸化联系起来的交叉对话。
