title: Alternate transcripts of the Drosophila "activator" E2F are necessary for maintenance of cell cycle exit during development.
abstract: The E2F family of transcription factors are evolutionarily conserved regulators of the cell cycle that can be divided into two groups based on their ability to either activate or repress transcription. In Drosophila, there is only one "activator" E2F, dE2F1, which provides all of the pro-proliferative activity of E2F during development. Interestingly, the de2f1 gene can be transcribed from multiple promoters resulting in six alternate transcripts. In this study, we sought to investigate the biological significance of the alternate transcriptional start sites. We focused on the de2f1 promoter region where tissue and cell-type specific enhancer activities were observed at the larval stage. While a genomic deletion of this region, de2f1(ΔRA), decreased the overall expression level of dE2F1, flies developed normally with no obvious proliferation defects. However, a detailed analysis of the de2f1(ΔRA) mutant eye imaginal discs revealed that dE2F1 is needed for proper cell cycle exit. We discovered that dE2F1 expression during G1 arrest prior to the differentiation process of the developing eye is important for maintaining cell cycle arrest at a later stage of the eye development. Overall, our study suggests that specific alternate transcripts of "activator" E2F, dE2F1, may have a dual function on cell cycle progression and cannot simply be viewed as a pro-proliferative transcription factor.
authors: Department of Biology, Developmental Biology Research Initiative, McGill University, Montreal, Quebec, Canada H3A 1B1.
authors: Mary-Rose
authors: MR
authors: Bradley-Gill
authors: Department of Biology, Developmental Biology Research Initiative, McGill University, Montreal, Quebec, Canada H3A 1B1.
authors: Minhee
authors: M
authors: Kim
authors: Department of Biology, Developmental Biology Research Initiative, McGill University, Montreal, Quebec, Canada H3A 1B1.
authors: Daniel
authors: D
authors: Feingold
authors: Department of Biology, Developmental Biology Research Initiative, McGill University, Montreal, Quebec, Canada H3A 1B1.
authors: Christine
authors: C
authors: Yergeau
authors: Department of Biology, Developmental Biology Research Initiative, McGill University, Montreal, Quebec, Canada H3A 1B1.
authors: Josée
authors: J
authors: Houde
authors: Department of Biology, Developmental Biology Research Initiative, McGill University, Montreal, Quebec, Canada H3A 1B1. Electronic address: nam.moon@mcgill.ca.
authors: Nam-Sung
authors: NS
authors: Moon
mesh_terms: D000818:Animals; D002453:Cell Cycle; D002454:Cell Differentiation; D002455:Cell Division; D003433:Crosses, Genetic; D029721:Drosophila Proteins / Q000235:genetics* / Q000502:physiology*; D004331:Drosophila melanogaster / Q000235:genetics*; D050684:E2F Transcription Factors / Q000235:genetics* / Q000502:physiology*; D005123:Eye / Q000196:embryology; D016193:G1 Phase; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D009154:Mutation; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors; D014158:Transcription, Genetic
chemical_list: D029721:Drosophila Proteins; D050684:E2F Transcription Factors; C496298:E2f1 protein, Drosophila; D014157:Transcription Factors
keywords: Cell cycle; Drosophila; E2F; Eye development