Rbf1-independent termination of E2f1-target gene expression during early Drosophila embryogenesis

Development. 2007 Feb;134(3):467-78. doi: 10.1242/dev.02738. Epub 2006 Dec 21.

Abstract

The initiation and maintenance of G1 cell cycle arrest is a key feature of animal development. In the Drosophila ectoderm, G1 arrest first appears during the seventeenth embryonic cell cycle. The initiation of G1(17) arrest requires the developmentally-induced expression of Dacapo, a p27-like Cyclin E-Cdk2 inhibitor. The maintenance of G1(17) arrest requires Rbf1-dependent repression of E2f1-regulated replication factor genes, which are expressed continuously during cycles 1-16 when S phase immediately follows mitosis. The mechanisms that trigger Rbf1 repressor function and mediate G1(17) maintenance are unknown. Here we show that the initial downregulation of expression of the E2f1-target gene RnrS, which occurs during cycles 15 and 16 prior to entry into G1(17), does not require Rbf1 or p27(Dap). This suggests a mechanism for Rbf1-independent control of E2f1 during early development. We show that E2f1 protein is destroyed in a cell cycle-dependent manner during S phase of cycles 15 and 16. E2f1 is destroyed during early S phase, and requires ongoing DNA replication. E2f1 protein reaccumulates in epidermal cells arrested in G1(17), and in these cells the induction of p27(Dap) activates Rbf1 to repress E2f1-target genes to maintain a stable G1 arrest.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Cycle
  • Cyclin E / metabolism
  • Cyclin-Dependent Kinase 2 / antagonists & inhibitors
  • Drosophila / cytology
  • Drosophila / embryology*
  • Drosophila / genetics
  • Drosophila / metabolism*
  • Drosophila Proteins / antagonists & inhibitors
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • E2F1 Transcription Factor / genetics
  • E2F1 Transcription Factor / metabolism*
  • Epidermal Cells
  • Epidermis / embryology
  • Epidermis / metabolism
  • G1 Phase
  • Gene Expression Regulation, Developmental
  • Genes, Insect
  • Mutation
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Phosphorylation
  • Retinoblastoma Protein
  • S Phase
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Cyclin E
  • Drosophila Proteins
  • E2F1 Transcription Factor
  • Nuclear Proteins
  • Rbf protein, Drosophila
  • Retinoblastoma Protein
  • Transcription Factors
  • dap protein, Drosophila
  • Cyclin-Dependent Kinase 2
  • cdk2 protein, Drosophila