Drosophila C/EBP: a tissue-specific DNA-binding protein required for embryonic development.

TitleDrosophila C/EBP: a tissue-specific DNA-binding protein required for embryonic development.
Publication TypeJournal Article
Year of Publication1992
AuthorsRørth P, Montell DJ
JournalGenes Dev
Volume6
Issue12A
Pagination2299-311
Date Published1992 Dec
ISSN0890-9369
KeywordsAmino Acid Sequence, Animals, Base Sequence, Blotting, Northern, CCAAT-Enhancer-Binding Proteins, Cloning, Molecular, DNA, DNA-Binding Proteins, Drosophila melanogaster, Escherichia coli, Germ Cells, Molecular Sequence Data, Nuclear Proteins, Organ Specificity, Promoter Regions, Genetic, Protein Binding, Restriction Mapping, Sequence Homology, Amino Acid, Transcription Factors, Transformation, Genetic
Abstract

<p>Recently, we reported the cloning of the Drosophila melanogaster homolog of the vertebrate CCAAT/enhancer-binding protein (C/EBP). Here, we describe studies of the DNA-binding and dimerization properties of Drosophila C/EBP (DmC/EBP), as well as its tissue distribution, developmental regulation, and essential role in embryonic development and conclude that it bears functional as well as structural similarity to mammalian C/EBP. DmC/EBP contains a basic region/leucine zipper (bZIP) DNA-binding domain very similar to that of mammalian C/EBP and the purified C/EBPs bound to DNA with the same sequence specificity. Among the DNA sequences that DmC/EBP bound with high affinity was a conserved site within the promoter of the DmC/EBP gene itself. In vitro, DmC/EBP and mammalian C/EBP specifically formed functional heterodimers; however, as we found no evidence for a family of DmC/EBPs, DmC/EBP may function as a homodimer in vivo. The DmC/EBP protein was expressed predominantly during late embryogenesis in the nuclei of a restricted set of differentiating cell types, such as the lining of the gut and epidermis, similar to the mammalian tissues that express C/EBP. We have characterized mutations in the DmC/EBP gene and found that deleting the gene caused late embryonic lethality. Embryos that lack C/EBP die just before or just upon hatching. The lethal phenotype of C/EBP mutants can be rescued with the cloned C/EBP gene introduced by P-element-mediated germ-line transformation. The strict requirement for C/EBP during Drosophila embryogenesis, coupled with its structural and functional similarities to mammalian C/EBP, provides a useful genetic system in which to study the role of C/EBP in development.</p>

DOI10.1101/gad.6.12a.2299
Alternate JournalGenes Dev.
PubMed ID1459454
Grant ListR01 AG063907 / AG / NIA NIH HHS / United States
R29GM46425 / GM / NIGMS NIH HHS / United States