Department of Biochemistry, Purdue University, West Lafayette, Indiana, USA.
Purdue University Center for Cancer Research, Purdue University, West Lafayette, Indiana, USA.
Insect Mol Biol. 2022 Dec;31(6):734-746. doi: 10.1111/imb.12800. Epub 2022 Jul 15.
Chiffon is the sole Drosophila ortholog of Dbf4, the regulatory subunit for the cell-cycle kinase Cdc7 that initiates DNA replication. In Drosophila, the chiffon gene encodes two polypeptides with independent activities. Chiffon-A contains the conserved Dbf4 motifs and interacts with Cdc7 to form the Dbf4-dependent Kinase (DDK) complex, which is essential for a specialized form of DNA replication. In contrast, Chiffon-B binds the histone acetyltransferase Gcn5 to form the Chiffon histone acetyltransferase (CHAT) complex, which is necessary for histone H3 acetylation and viability. Previous studies have shown that the Chiffon-B region is only present within insects. However, it was unclear how widely the interaction between Chiffon-B and Gcn5 was conserved among insect species. To examine this, we performed yeast two-hybrid assays using Chiffon-B and Gcn5 from a variety of insect species and found that Chiffon-B and Gcn5 interact in Diptera species such as Australian sheep blowfly and yellow fever mosquito. Protein domain analysis identified that Chiffon-B has features of acidic transcriptional activators such as Gal4 or VP16. We propose that the CHAT complex plays a critical role in a biological process that is unique to Dipterans and could therefore be a potential target for pest control strategies.
缎纹是果蝇的唯一直系同源物,是启动 DNA 复制的细胞周期激酶 Cdc7 的调节亚基。在果蝇中,缎纹基因编码两种具有独立活性的多肽。Chiffon-A 含有保守的 Dbf4 基序,并与 Cdc7 相互作用形成 Dbf4 依赖性激酶(DDK)复合物,这对于一种特殊形式的 DNA 复制是必不可少的。相比之下,Chiffon-B 结合组蛋白乙酰转移酶 Gcn5 形成缎纹组蛋白乙酰转移酶(CHAT)复合物,这对于组蛋白 H3 乙酰化和生存力是必需的。先前的研究表明,Chiffon-B 区域仅存在于昆虫中。然而,Chiffon-B 和 Gcn5 之间的相互作用在昆虫物种中是如何广泛保守的尚不清楚。为了研究这一点,我们使用来自各种昆虫物种的 Chiffon-B 和 Gcn5 进行了酵母双杂交测定,发现 Chiffon-B 和 Gcn5 在澳大利亚绵羊苍蝇和黄热病蚊子等双翅目物种中相互作用。蛋白结构域分析表明,Chiffon-B 具有 Gal4 或 VP16 等酸性转录激活因子的特征。我们提出 CHAT 复合物在双翅目特有的生物学过程中起着关键作用,因此可能成为害虫防治策略的潜在目标。