title: string(cdc25) and cyclin E are required for patterned histone expression at different stages of Drosophila embryonic development.
abstract: Metazoan replication-dependent histone mRNAs accumulate to high levels during S phase as a result of an increase in the rate of histone gene transcription, pre-mRNA processing, and mRNA stability at the G1-S transition. However, relatively little is known about the contribution of these processes to histone expression in the cell cycles of early development, which often lack a G1 phase. In post-blastoderm Drosophila embryos, zygotic expression of the stg(cdc25) phosphatase in G2 activates cyclin/cdc2 kinases and triggers mitosis. Here we show that histone transcription initiates in late G2 of cycle 14 in response to stg(cdc25) and in anticipation of S phase of the next cycle, which occurs immediately following mitosis. Mutation of stg(cdc25) arrests cells in G2 and prevents histone transcription. Expression of a mutant form of Cdc2 that bypasses the requirement for stg(cdc25) activates histone transcription during G2 in stg(cdc25) mutant embryos. Thus, in these embryonic cycles, histone transcription is controlled by the principal G2-M regulators, string(cdc25), and cdc2 kinase, rather than solely by regulators of the G1-S transition. After the introduction of G1-S control midway through embryogenesis, histone expression depends on DNA replication and the function of cyclin E, and no longer requires stg(cdc25). Thus, during the altered cell cycles of early animal development, different cell cycle mechanisms are employed to ensure that the production of histones accompanies DNA synthesis.
authors.affiliation: Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Lanzotti
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Kupsco
authors.forename: William F
authors.initials: WF
authors.lastname: Marzluff
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Duronio
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins; D019927:Cyclin E / Q000378:metabolism*; D017931:DNA Primers; D004261:DNA Replication / Q000502:physiology; D004330:Drosophila / Q000196:embryology* / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006657:Histones / Q000378:metabolism*; D017403:In Situ Hybridization; D016133:Polymerase Chain Reaction; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D019927:Cyclin E; D017931:DNA Primers; D029721:Drosophila Proteins; D006657:Histones; D016203:CDC2 Protein Kinase; D017027:Protein Tyrosine Phosphatases; C059217:stg protein, Drosophila; D001973:Bromodeoxyuridine