Tissue-specific regulation of cyclin E transcription during Drosophila melanogaster embryogenesis.

Cyclin E is an essential regulator of S phase entry. We have previously shown that transcriptional regulation of the gene that encodes Drosophila cyclin E, DmcycE, plays an important role in the control of the G(1) to S phase transition during development. We report here the first comprehensive analysis of the transcriptional regulation of a G(1 )phase cell cycle regulatory gene during embryogenesis. Analysis of deficiencies, a genomic transformant and reporter gene constructs revealed that DmcycE transcription is controlled by a large and complex cis-regulatory region containing tissue- and stage-specific components. Separate regulatory elements for transcription in epidermal cells during cell cycles 14-16, central nervous system cells and peripheral nervous system cells were found. An additional cis-regulatory element drives transcription in thoracic epidermal cells that undergo a 17th cell cycle when other epidermal cells have arrested in G(1 )phase prior to terminal differentiation. The complexity of DmcycE transcriptional regulation argues against a model in which DmcycE transcription is regulated simply and solely by G(1) to S phase transcription regulators such as RB, E2F and DP. Rather, our study demonstrates that tissue-specific transcriptional regulatory mechanisms are important components of the control of cyclin E transcription and thus of cell proliferation in metazoans.

[1]  R. Duronio,et al.  Cell cycle: To differentiate or not to differentiate? , 2000, Current Biology.

[2]  H. Vaessin,et al.  Pan-neural Prospero terminates cell proliferation during Drosophila neurogenesis. , 2000, Genes & development.

[3]  J. S. Britton,et al.  Cis-regulatory elements of the mitotic regulator, string/Cdc25. , 1999, Development.

[4]  N. Dyson,et al.  The role of RBF in the introduction of G1 regulation during Drosophila embryogenesis , 1999, The EMBO journal.

[5]  J. Horsfield,et al.  decapentaplegic is required for arrest in G1 phase during Drosophila eye development. , 1998, Development.

[6]  T. Sawado,et al.  dE2F2, a novel E2F-family transcription factor in Drosophila melanogaster. , 1998, Biochemical and biophysical research communications.

[7]  N. Dyson.  The regulation of E2F by pRB-family proteins. , 1998, Genes & development.

[8]  H. Richardson,et al.  Analysis of a Drosophila cyclin E hypomorphic mutation suggests a novel role for cyclin E in cell proliferation control during eye imaginal disc development. , 1998, Genetics.

[9]  B. Edgar,et al.  Wingless and Notch regulate cell-cycle arrest in the developing Drosophila wing , 1998, Nature.

[10]  S. Artavanis-Tsakonas,et al.  Cell proliferation control by Notch signaling in Drosophila development. , 1998, Development.

[11]  K. Fazekas.  [Regulation of the cell cycle]. , 1998, Orvosi hetilap.

[12]  H. Reichert,et al.  The wingless gene is required for embryonic brain development in Drosophila , 1998, Development Genes and Evolution.

[13]  C. Lehner,et al.  Continuous Cyclin E expression inhibits progression through endoreduplication cycles in Drosophila , 1998, Current Biology.

[14]  P. O’Farrell,et al.  Fluctuations in Cyclin E levels are required for multiple rounds of endocycle S phase in Drosophila , 1998, Current Biology.

[15]  P. O’Farrell,et al.  Mutations of the Drosophila dDP,dE2F, and cyclin E Genes Reveal Distinct Roles for the E2F-DP Transcription Factor and Cyclin E during the G1-S Transition , 1998, Molecular and Cellular Biology.

[16]  I. Royzman,et al.  Mutations in Drosophila DP and E2F distinguish G1-S progression from an associated transcriptional program. , 1997, Genes & development.

[17]  P. O’Farrell,et al.  Limb morphogenesis: connections between patterning and growth , 1997, Current Biology.

[18]  P. O’Farrell,et al.  Cdks and the Drosophila cell cycle. , 1997, Current opinion in genetics & development.

[19]  P. O’Farrell,et al.  E2F-induced S phase requires cyclin E. , 1996, Genes & development.

[20]  S. Reed,et al.  G1/S regulatory mechanisms from yeast to man. , 1996, Progress in cell cycle research.

[21]  C. Lehner,et al.  Cell fate specification by even-skipped expression in the Drosophila nervous system is coupled to cell cycle progression. , 1995, Development.

[22]  T Marty,et al.  Ectopic cyclin E expression induces premature entry into S phase and disrupts pattern formation in the Drosophila eye imaginal disc. , 1995, Development.

[23]  M. Akam,et al.  How the Hox gene Ultrabithorax specifies two different segments: the significance of spatial and temporal regulation within metameres. , 1995, Development.

[24]  P. O’Farrell,et al.  Developmental control of the G1 to S transition in Drosophila: cyclin Eis a limiting downstream target of E2F. , 1995, Genes & development.

[25]  C. Lehner,et al.  Distinct modes of cyclin E/cdc2c kinase regulation and S-phase control in mitotic and endoreduplication cycles of Drosophila embryogenesis. , 1995, Genes & development.

[26]  James M. Roberts,et al.  Human cyclin E, a nuclear protein essential for the G1-to-S phase transition , 1995, Molecular and cellular biology.

[27]  P. O’Farrell,et al.  Transcriptional regulation of string (cdc25): a link between developmental programming and the cell cycle. , 1994, Development.

[28]  C. Lehner,et al.  Cyclin E controls S phase progression and its down-regulation during Drosophila embryogenesis is required for the arrest of cell proliferation , 1994, Cell.

[29]  M. Gossen,et al.  Acceleration of the G1/S phase transition by expression of cyclins D1 and E with an inducible system. , 1994, Molecular and cellular biology.

[30]  S. Reed,et al.  A Drosophila G1-specific cyclin E homolog exhibits different modes of expression during embryogenesis. , 1993, Development.

[31]  James M. Roberts,et al.  Cyclin-dependent regulation of G1 in mammalian fibroblasts. , 1993, Science.

[32]  A. M. Arias,et al.  The wingless product is required for cell proliferation in the Malpighian tubule anlage of Drosophila melanogaster , 1992 .

[33]  T. Kaufman,et al.  Homeotic genes have specific functional roles in the establishment of the Drosophila embryonic peripheral nervous system. , 1992, Development.

[34]  S. Reed,et al.  The role of p34 kinases in the G1 to S-phase transition. , 1992, Annual review of cell biology.

[35]  T. Hunter,et al.  Cyclin-dependent kinases: a new cell cycle motif? , 1991, Trends in cell biology.

[36]  T. Orr-Weaver,et al.  The regulation of the cell cycle during Drosophila embryogenesis: the transition to polyteny. , 1991, Development.

[37]  M. Bate,et al.  The embryonic origin of imaginal discs in Drosophila. , 1991, Development.

[38]  F. Hoffmann,et al.  Pattern-specific expression of the Drosophila decapentaplegic gene in imaginal disks is regulated by 3' cis-regulatory elements. , 1990, Genes & development.

[39]  P. O’Farrell,et al.  The three postblastoderm cell cycles of Drosophila embryogenesis are regulated in G2 by string , 1990, Cell.

[40]  P. O’Farrell,et al.  Genetic control of cell division patterns in the Drosophila embryo , 1989, Cell.

[41]  V. Foe,et al.  Mitotic domains reveal early commitment of cells in Drosophila embryos. , 1989, Development.