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CAF-1 is essential for Drosophila development and involved in the maintenance of epigenetic memory.
- Source :
-
Developmental biology [Dev Biol] 2007 Nov 01; Vol. 311 (1), pp. 213-22. Date of Electronic Publication: 2007 Aug 29. - Publication Year :
- 2007
-
Abstract
- DNA synthesis during S-phase and upon DNA repair is accompanied by chromatin assembly. The chromatin assembly factor CAF-1 has been biochemically well-characterized to deposit histones onto newly synthesized DNA. To gain insights into the in vivo functions of CAF-1 in Drosophila, we generated null mutants of the largest subunit of dCAF-1, dCAF-1-p180. We show that, unlike CAF-1 mutant yeast, dCAF-1-p180 mutant flies are hemizygous lethal. Removal of maternal dCAF-1-p180 activity by germline clones blocks oogenesis. Tissue-specific deletion of dCAF-1-p180 in the eye primordia disrupts eye development. In addition, reduction of dCAF-1-p180 activity suppresses gene silencing at heterochromatin and antagonizes Polycomb-mediated cell fate determination. Furthermore, heterozygous dCAF-1-p180 mutant flies display an increased sensitivity to gamma-irradiation and a reduced efficiency in recombinational double strand break (DSB) repair. Our experiments also show that human hCAF-1-p150 can rescue the dCAF-1-p180 mutant flies, demonstrating a functional conservation of eukaryotic CAF-1 activities in vivo. Together, our results establish that dCAF-1-p180 is an essential gene for Drosophila development and further underscore the importance of dCAF-1 in regulating gene expression and DNA repair in vivo.
- Subjects :
- Animals
Animals, Genetically Modified
Chromosomal Proteins, Non-Histone genetics
Drosophila Proteins genetics
Drosophila melanogaster metabolism
Eye embryology
Female
Gene Silencing
Male
Molecular Chaperones genetics
Mutagenesis
Retinoblastoma-Binding Protein 4
Transcription Factors genetics
Chromosomal Proteins, Non-Histone metabolism
Drosophila Proteins metabolism
Drosophila melanogaster embryology
Epigenesis, Genetic
Molecular Chaperones metabolism
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1095-564X
- Volume :
- 311
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Developmental biology
- Publication Type :
- Academic Journal
- Accession number :
- 17916346
- Full Text :
- https://doi.org/10.1016/j.ydbio.2007.08.039