Developmentally regulated histone modifications in Drosophila follicle cells: initiation of gene amplification is associated with histone H3 and H4 hyperacetylation and H1 phosphorylation
- First Online:
We have used gene amplification in Drosophila follicle cells as a model of metazoan DNA replication to address whether changes in histone modifications are associated with replication origin activation. We observe that replication initiation is associated with distinct histone modifications. Acetylated lysines K5, K8, and K12 on histone H4 and K14 on histone H3 are specifically enriched during replication initiation at the amplification origins. Strikingly, H4 acetylation persists at an amplification origin well after replication forks have progressed significantly outward from the origin, indicating that H4 acetylation is associated with origin regulation and not histone deposition at the replication forks. Origin recognition complex subunit 2 (orc2) mutants with severe amplification defects do not abolish H4 acetylation, whereas the dup/cdt1 mutant delays the appearance of acetylation foci, and mutants in rbf result in temporal persistence. These data indicate that core histone acetylation is associated with origin activity. Furthermore, follicle cells undergoing gene amplification exhibit high levels of histone H1 phosphorylation. The patterns of H1 phosphorylation provide insights into cell cycle states during amplification, as H1 kinase activity in follicle cells is responsive to high Cyclin E activity, and it can be abolished by overexpressing the retinoblastoma homolog, Rbf, that represses Cyclin E. These data suggest that amplification origins are able to initiate when the cells are in a late S-phase, when the genome is normally not licensed for replication.
- Foe VE, Odell GM, Edgar BA (1993) Mitosis and morphogenesis in the Drosophila embryo: point and counterpoint. In: Bate M, Martinez Arias A (eds) The development of Drosophila melanogaster. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, pp 149–300Google Scholar
- Hendzel MJ, Wei Y, Mancini MA, Van Hooser A, Ranalli T, Brinkley BR, Bazett-Jones DP, Allis CD (1997) Mitosis-specific phosphorylation of histone H3 initiates primarily within pericentromeric heterochromatin during G2 and spreads in an ordered fashion coincident with mitotic chromosome condensation. Chromosoma 106:348–360PubMedCrossRefGoogle Scholar
- Parks S, Spradling A (1987) Spatially regulated expression of chorion genes during Drosophila oogenesis. Genes Dev 1:497–509Google Scholar
- Spradling AC (1993) Developmental genetics of oogenesis. In: Bate M, Martinez Arias A (eds) The development of Drosophila melanogaster. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, pp 1–70Google Scholar