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J Cell Sci. 2019 Jan 16;132(2). pii: jcs214072. doi: 10.1242/jcs.214072.

The Drosophila Dbf4 ortholog Chiffon forms a complex with Gcn5 that is necessary for histone acetylation and viability.

Author information

1
Department of Biochemistry, Purdue University, West Lafayette, IN 47907, USA.
2
Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA.
3
Stowers Institute for Medical Research, 1000 E. 50th St., Kansas City, MO 64110, USA.
4
Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.
5
Department of Biochemistry, Purdue University, West Lafayette, IN 47907, USA vweake@purdue.edu.
6
Purdue University Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA.

Abstract

Metazoans contain two homologs of the Gcn5-binding protein Ada2, Ada2a and Ada2b, which nucleate formation of the ATAC and SAGA complexes, respectively. In Drosophila melanogaster, 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 Drosophila 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 chiffon 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 chiffon 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.

KEYWORDS:

Cell cycle; Dbf4; Gcn5; Gene expression; Histone acetylation

PMID:
30559249
DOI:
10.1242/jcs.214072

Conflict of interest statement

Competing interestsThe authors declare no competing or financial interests.

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