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ABSTRACT The histone acetyltransferase Gcn5 is critical for gene expression and development. In Drosophila, Gcn5 is part of four complexes (SAGA, ATAC, CHAT and ADA) that are essential for fly viability and have key roles in regulating gene expression. Here, we show that although the SAGA, ADA and CHAT complexes play redundant roles in embryonic gene expression, the insect-specific CHAT complex uniquely regulates expression of a subset of developmental genes. We also identify a substantial decrease in histone acetylation in chiffon mutant embryos that exceeds that observed in Ada2b, suggesting broader roles for Chiffon in regulating histone acetylation outside of the Gcn5 complexes. The chiffon gene encodes two independent polypeptides that nucleate formation of either the CHAT or Dbf4-dependent kinase (DDK) complexes. DDK includes the cell cycle kinase Cdc7, which is necessary for maternally driven DNA replication in the embryo. We identify a temporal switch between the expression of these chiffon gene products during a short window during the early nuclear cycles in embryos that correlates with the onset of zygotic genome activation, suggesting a potential role for CHAT in this process. This article has an associated First Person interview with the first author of the paper.
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The interaction between the Dbf4 ortholog Chiffon and Gcn5 is conserved in Dipteran insect species
Abstract Chiffon is the soleDrosophilaortholog of Dbf4, the regulatory subunit for the cell‐cycle kinase Cdc7 that initiates DNA replication. InDrosophila, thechiffongene 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.
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- Award ID(s):
- 1930237
- PAR ID:
- 10368856
- Publisher / Repository:
- Wiley-Blackwell
- Date Published:
- Journal Name:
- Insect Molecular Biology
- Volume:
- 31
- Issue:
- 6
- ISSN:
- 0962-1075
- Page Range / eLocation ID:
- p. 734-746
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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