Department of Biochemistry, Purdue University, West Lafayette, IN 47907, USA.
Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA.
J Cell Sci. 2019 Jan 16;132(2):jcs214072. doi: 10.1242/jcs.214072.
Metazoans contain two homologs of the Gcn5-binding protein Ada2, Ada2a and Ada2b, which nucleate formation of the ATAC and SAGA complexes, respectively. In , there are two splice isoforms of Ada2b: Ada2b-PA and Ada2b-PB. Here, we show that only the Ada2b-PB isoform is in SAGA; in contrast, Ada2b-PA associates with Gcn5, Ada3, Sgf29 and Chiffon, forming the Chiffon histone acetyltransferase (CHAT) complex. Chiffon is the ortholog of Dbf4, which binds and activates the cell cycle kinase Cdc7 to initiate DNA replication. In flies, Chiffon and Cdc7 are required in ovary follicle cells for gene amplification, a specialized form of DNA re-replication. Although was previously reported to be dispensable for viability, here, we find that Chiffon is required for both histone acetylation and viability in flies. Surprisingly, we show that is a dicistronic gene that encodes distinct Cdc7- and CHAT-binding polypeptides. Although the Cdc7-binding domain of Chiffon is not required for viability in flies, the CHAT-binding domain is essential for viability, but is not required for gene amplification, arguing against a role in DNA replication.
后生动物含有两个 Gcn5 结合蛋白 Ada2 的同源物，Ada2a 和 Ada2b，它们分别启动 ATAC 和 SAGA 复合物的形成。在 中，Ada2b 有两种剪接异构体：Ada2b-PA 和 Ada2b-PB。在这里，我们表明只有 Ada2b-PB 异构体存在于 SAGA 中；相比之下，Ada2b-PA 与 Gcn5、Ada3、Sgf29 和 Chiffon 结合，形成 Chiffon 组蛋白乙酰转移酶 (CHAT) 复合物。Chiffon 是 Dbf4 的直系同源物，它与细胞周期激酶 Cdc7 结合并激活，以启动 DNA 复制。在果蝇中，Chiffon 和 Cdc7 在卵巢滤泡细胞中对于基因扩增（一种特殊形式的 DNA 再复制）是必需的。虽然以前报道 对于生存力是可有可无的，但在这里，我们发现 Chiffon 在果蝇中既需要组蛋白乙酰化也需要生存力。令人惊讶的是，我们表明 是一个二顺反子基因，编码不同的 Cdc7 和 CHAT 结合多肽。虽然 Chiffon 的 Cdc7 结合域对于果蝇的生存力不是必需的，但 CHAT 结合域对于生存力是必不可少的，但对于基因扩增不是必需的，这表明它在 DNA 复制中不起作用。
