GAGA mediates the enhancer blocking activity of the eve promoter in the Drosophila embryo.

Insulator DNAs and promoter competition regulate enhancer-promoter interactions within complex genetic loci. A transgenic embryo assay was used to obtain evidence that the Drosophila eve promoter possesses an insulator activity that can be uncoupled from the core elements that mediate competition. The eve promoter contains an optimal TATA element and a GAGA sequence. The analysis of various chimeric promoters provides evidence that TATA is essential for promoter competition, whereas GAGA mediates enhancer blocking. The Trithorax-like (Trl) protein interacts with GAGA, and mutations in trl attenuate eve promoter insulator activity. We suggest that Trl-GAGA increases the stability of enhancer-promoter interactions by creating an open chromatin configuration at the core promoter.

[1]  Alexander F. Schier,et al.  Direct homeodomain–DNA interaction in the autoregulation of the fushi tarazu gene , 1992, Nature.

[2]  P. C. Wensink,et al.  Insulating DNA directs ubiquitous transcription of the Drosophila melanogaster alpha 1-tubulin gene , 1994, Molecular and cellular biology.

[3]  P. Geyer,et al.  Effects of the su(Hw) insulator protein on the expression of the divergently transcribed Drosophila yolk protein genes. , 1995, The EMBO journal.

[4]  M. Levine,et al.  Regulation of even‐skipped stripe 2 in the Drosophila embryo. , 1992, The EMBO journal.

[5]  T. Burke,et al.  The downstream core promoter element, DPE, is conserved from Drosophila to humans and is recognized by TAFII60 of Drosophila. , 1997, Genes & development.

[6]  T. Tsukiyama,et al.  Chromatin remodeling and transcription. , 1997, Current opinion in genetics & development.

[7]  F. Karch,et al.  The Trithorax-like gene encodes the Drosophila GAGA factor , 1994, Nature.

[8]  P. Schedl,et al.  Fab-7 functions as a chromatin domain boundary to ensure proper segment specification by the Drosophila bithorax complex. , 1996, Genes & development.

[9]  J. D. Engel,et al.  Developmental regulation of β-globin gene switching , 1988, Cell.

[10]  S. Smale,et al.  Transcription initiation from TATA-less promoters within eukaryotic protein-coding genes. , 1997, Biochimica et biophysica acta.

[11]  Y. Hérault,et al.  Ulnaless (Ul), a regulatory mutation inducing both loss-of-function and gain-of-function of posterior Hoxd genes. , 1997, Development.

[12]  T. Burke,et al.  Drosophila TFIID binds to a conserved downstream basal promoter element that is present in many TATA-box-deficient promoters. , 1996, Genes & development.

[13]  F. Karch,et al.  In situ dissection of the Fab-7 region of the bithorax complex into a chromatin domain boundary and a Polycomb-response element. , 1997, Development.

[14]  J. Lis,et al.  Dynamics of potentiation and activation: GAGA factor and its role in heat shock gene regulation. , 1997, Nucleic acids research.

[15]  S. Henikoff.  Dosage-dependent modification of position-effect variegation in Drosophila. , 1996, BioEssays : news and reviews in molecular, cellular and developmental biology.

[16]  M. Levine,et al.  Different core promoters possess distinct regulatory activities in the Drosophila embryo. , 1998, Genes & development.

[17]  D Kosman,et al.  The dorsal morphogen gradient regulates the mesoderm determinant twist in early Drosophila embryos. , 1991, Genes & development.

[18]  E. Lewis,et al.  Complete sequence of the bithorax complex of Drosophila. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[19]  R. Krumlauf,et al.  Selectivity, sharing and competitive interactions in the regulation of Hoxb genes , 1998, The EMBO journal.

[20]  Paul Schedl,et al.  A position-effect assay for boundaries of higher order chromosomal domains , 1991, Cell.

[21]  V. Corces,et al.  DNA position-specific repression of transcription by a Drosophila zinc finger protein. , 1992, Genes & development.

[22]  Victor G Corces,et al.  Polycomb and Trithorax Group Proteins Mediate the Function of a Chromatin Insulator , 1998, Cell.

[23]  D. Dorsett.  Distance-independent inactivation of an enhancer by the suppressor of Hairy-wing DNA-binding protein of Drosophila. , 1993, Genetics.

[24]  G. Marius Clore,et al.  The solution structure of a specific GAGA factor–DNA complex reveals a modular binding mode , 1997, Nature Structural Biology.

[25]  F. Karch,et al.  The GAGA factor is required in the early Drosophila embryo not only for transcriptional regulation but also for nuclear division. , 1996, Development.

[26]  P. Geyer,et al.  The role of insulator elements in defining domains of gene expression. , 1997, Current opinion in genetics & development.

[27]  V. Corces,et al.  A drosophila protein that imparts directionality on a chromatin insulator is an enhancer of position-effect variegation , 1995, Cell.

[28]  I. Arkhipova,et al.  Promoter elements in Drosophila melanogaster revealed by sequence analysis. , 1995, Genetics.

[29]  R. Kellum,et al.  A group of scs elements function as domain boundaries in an enhancer-blocking assay , 1992, Molecular and cellular biology.

[30]  A. Udvardy,et al.  Genetic and molecular analysis of chromatin domains. , 1993, Cold Spring Harbor symposia on quantitative biology.

[31]  A. Laughon,et al.  Sequence of a Drosophila segmentation gene: protein structure homology with DNA-binding proteins , 1984, Nature.

[32]  M. Levine,et al.  The Fab-7 element of the bithorax complex attenuates enhancer-promoter interactions in the Drosophila embryo. , 1996, Genes & development.

[33]  M. Levine,et al.  Modulation of enhancerá¤-promoter interactions by insulators in the Drosophilaembryo , 1995, Nature.

[34]  J. D. Engel,et al.  Individual stage selector element mutations lead to reciprocal changes in beta- vs. epsilon-globin gene transcription: genetic confirmation of promoter competition during globin gene switching. , 1992, Genes & development.

[35]  A. Schier,et al.  Analysis of the ftz upstream element: germ layer-specific enhancers are independently autoregulated. , 1990, Genes & development.

[36]  T. Kaufman,et al.  Genetic analysis of embryonic cis-acting regulatory elements of the Drosophila homeotic gene sex combs reduced. , 1995, Genetics.