Dissecting the regulatory switches of development: lessons from enhancer evolution in Drosophila

Cis-regulatory modules are non-protein-coding regions of DNA essential for the control of gene expression. One class of regulatory modules is embryonic enhancers, which drive gene expression during development as a result of transcription factor protein binding at the enhancer sequences. Recent comparative studies have begun to investigate the evolution of the sequence architecture within enhancers. These analyses are illuminating the way that developmental biologists think about enhancers by revealing their molecular mechanism of function.

[1]  D. Arnosti,et al.  Information display by transcriptional enhancers , 2003, Development.

[2]  L. Madisen,et al.  The Immunoglobulin Heavy Chain Locus Control Region Increases Histone Acetylation along Linked c-myc Genes , 1998, Molecular and Cellular Biology.

[3]  R. Steward,et al.  The dorsal protein is distributed in a gradient in early drosophila embryos , 1988, Cell.

[4]  Justin Crocker,et al.  Evolution Acts on Enhancer Organization to Fine-Tune Gradient Threshold Readouts , 2008, PLoS biology.

[5]  V. Pirrotta,et al.  The bx region enhancer, a distant cis‐control element of the Drosophila Ubx gene and its regulation by hunchback and other segmentation genes. , 1991, The EMBO journal.

[6]  M. Kreitman,et al.  Evolutionary dynamics of the enhancer region of even-skipped in Drosophila. , 1995, Molecular biology and evolution.

[7]  M. Fujioka,et al.  A chromatin insulator mediates transgene homing and very long-range enhancer-promoter communication , 2009, Development.

[8]  William McGinnis,et al.  Hox protein mutation and macroevolution of the insect body plan , 2002, Nature.

[9]  P. Chambon,et al.  Stimulation of in vitro transcription from the SV40 early promoter by the enhancer involves a specific trans‐acting factor. , 1984, The EMBO journal.

[10]  K. Struhl Genetic properties and chromatin structure of the yeast gal regulatory element: an enhancer-like sequence. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[11]  C. Nüsslein-Volhard,et al.  A gradient of bicoid protein in Drosophila embryos , 1988, Cell.

[12]  Esther Bae,et al.  A novel promoter-tethering element regulates enhancer-driven gene expression at the bithorax complex in the Drosophila embryo , 2007, Development.

[13]  J. D. Engel,et al.  A 3′ enhancer is required for temporal and tissue-specific transcriptional activation of the chicken adult β-globin gene , 1986, Nature.

[14]  E. Lewis,et al.  The molecular genetics of the bithorax complex of Drosophila: cis‐regulation in the Abdominal‐B domain. , 1990, The EMBO journal.

[15]  Michael Levine,et al.  Promoter-proximal tethering elements regulate enhancer-promoter specificity in the Drosophila Antennapedia complex , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[16]  K. Dahlman-Wright,et al.  Direct interaction of the tau 1 transactivation domain of the human glucocorticoid receptor with the basal transcriptional machinery , 1993, Molecular and cellular biology.

[17]  S. Harrison,et al.  An Atomic Model of the Interferon-β Enhanceosome , 2007, Cell.

[18]  E. Lewis,et al.  The abdominal region of the bithorax complex , 1985, Cell.

[19]  S. Carroll,et al.  Repeated morphological evolution through cis-regulatory changes in a pleiotropic gene , 2006, Nature.

[20]  I. Talianidis,et al.  Coordination of PIC Assembly and Chromatin Remodeling During Differentiation-Induced Gene Activation , 2002, Science.

[21]  M. Levine,et al.  Transcriptional repression of eukaryotic promoters , 1989, Cell.

[22]  Esther Bae,et al.  Functional Evolution of cis-Regulatory Modules at a Homeotic Gene in Drosophila , 2009, PLoS genetics.

[23]  Walter J. Gehring,et al.  Control elements of the Drosophila segmentation gene fushi tarazu , 1985, Cell.

[24]  S. Carroll,et al.  Chance caught on the wing: cis-regulatory evolution and the origin of pigment patterns in Drosophila , 2005, Nature.

[25]  Venky N. Iyer,et al.  Sepsid even-skipped Enhancers Are Functionally Conserved in Drosophila Despite Lack of Sequence Conservation , 2008, PLoS genetics.

[26]  M. Levine,et al.  The eve stripe 2 enhancer employs multiple modes of transcriptional synergy. , 1996, Development.

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

[28]  M. Levine,et al.  The dorsal morphogen is a sequence-specific DNA-binding protein that interacts with a long-range repression element in drosophila , 1991, Cell.

[29]  D Bopp,et al.  The role of localization of bicoid RNA in organizing the anterior pattern of the Drosophila embryo. , 1988, The EMBO journal.

[30]  Sudhir Kumar,et al.  Temporal patterns of fruit fly (Drosophila) evolution revealed by mutation clocks. , 2003, Molecular biology and evolution.

[31]  P. Grant,et al.  Transcriptional activators direct histone acetyltransferase complexes to nucleosomes , 1998, Nature.

[32]  Pierre Chambon,et al.  In vivo sequence requirements of the SV40 early promoter region , 1981, Nature.

[33]  A. Dean,et al.  A Human Globin Enhancer Causes both Discrete and Widespread Alterations in Chromatin Structure , 2003, Molecular and Cellular Biology.

[34]  Mark Ptashne,et al.  Gene regulation by proteins acting nearby and at a distance , 1986, Nature.

[35]  H. Jäckle,et al.  Gene regulation in the Drosophila embryo. , 1996, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[36]  M. Levine,et al.  Short-range repression permits multiple enhancers to function autonomously within a complex promoter. , 1994, Genes & development.

[37]  N. Patel,et al.  Functional analysis of eve stripe 2 enhancer evolution in Drosophila: rules governing conservation and change. , 1998, Development.

[38]  K. Struhl,et al.  The gradient morphogen bicoid is a concentration-dependent transcriptional activator , 1989, Cell.

[39]  T. Maniatis,et al.  Virus induction of human IFNβ gene expression requires the assembly of an enhanceosome , 1995, Cell.

[40]  Francesca Chiaromonte,et al.  Transcriptional enhancement by GATA1-occupied DNA segments is strongly associated with evolutionary constraint on the binding site motif. , 2008, Genome research.

[41]  M. Levine,et al.  Transcriptional regulation of a pair-rule stripe in Drosophila. , 1991, Genes & development.

[42]  S. Jia,et al.  The Dorsal Rel Homology Domain Plays an Active Role in Transcriptional Regulation , 2002, Molecular and Cellular Biology.

[43]  S. Carroll,et al.  Regulation of Body Pigmentation by the Abdominal-B Hox Protein and Its Gain and Loss in Drosophila Evolution , 2006, Cell.

[44]  N. Patel,et al.  Evidence for stabilizing selection in a eukaryotic enhancer element , 2000, Nature.

[45]  M. Nóbrega,et al.  Scanning Human Gene Deserts for Long-Range Enhancers , 2003, Science.

[46]  Michael Levine,et al.  Sequence-specific DNA-binding activities of the gap proteins encoded by hunchback and Krüppel in Drosophila , 1989, Nature.

[47]  Michael B. Eisen,et al.  A Careful Look at Binding Site Reorganization in the even-skipped Enhancers of Drosophila and Sepsids , 2008, PLoS genetics.

[48]  Alan M. Moses,et al.  Conservation and Evolution of Cis-Regulatory Systems in Ascomycete Fungi , 2004, PLoS biology.

[49]  M. Hung,et al.  Developmental control of Drosophila yolk protein 1 gene by cis-acting DNA elements. , 1985, Cold Spring Harbor Symposia on Quantitative Biology.

[50]  Manolis Kellis,et al.  Whole-genome ChIP-chip analysis of Dorsal, Twist, and Snail suggests integration of diverse patterning processes in the Drosophila embryo. , 2007, Genes & development.

[51]  N. Dillon,et al.  Functional gene expression domains: defining the functional unit of eukaryotic gene regulation. , 2000, BioEssays : news and reviews in molecular, cellular and developmental biology.

[52]  M. Levine,et al.  Autoregulatory and gap gene response elements of the even‐skipped promoter of Drosophila. , 1989, The EMBO journal.

[53]  Yuzhong Cheng,et al.  Enhancer-promoter communication at the Drosophila engrailed locus , 2009, Development.

[54]  Michael B. Eisen,et al.  Big Genomes Facilitate the Comparative Identification of Regulatory Elements , 2009, PloS one.

[55]  M. Levine,et al.  Regulation of two pair-rule stripes by a single enhancer in the Drosophila embryo. , 1996, Developmental biology.

[56]  Justin Crocker,et al.  A Closer Look at the eve Stripe 2 Enhancers of Drosophila and Themira , 2008, PLoS genetics.

[57]  J. Banerji,et al.  A lymphocyte-specific cellular enhancer is located downstream of the joining region in immunoglobulin heavy chain genes , 1983, Cell.

[58]  Michael Levine,et al.  Coordinate enhancers share common organizational features in the Drosophila genome. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[59]  P. Ingham,et al.  Isolation, structure, and expression of even-skipped: A second pair-rule gene of Drosophila containing a homeo box , 1986, Cell.

[60]  E. Lewis A gene complex controlling segmentation in Drosophila , 1978, Nature.

[61]  S. Carroll,et al.  Emerging principles of regulatory evolution , 2007, Proceedings of the National Academy of Sciences.

[62]  James T Kadonaga,et al.  Regulation of RNA Polymerase II Transcription by Sequence-Specific DNA Binding Factors , 2004, Cell.

[63]  J. Banerji,et al.  Expression of a β-globin gene is enhanced by remote SV40 DNA sequences , 1981, Cell.

[64]  J. Banerji,et al.  Expression of a beta-globin gene is enhanced by remote SV40 DNA sequences. , 1981, Cell.

[65]  C. S. Parker,et al.  Transcriptional control of Drosophila fushi tarazu zebra stripe expression. , 1989, Genes & development.

[66]  E. Davidson,et al.  Modular cis-regulatory organization of developmentally expressed genes: two genes transcribed territorially in the sea urchin embryo, and additional examples. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[67]  Tom Maniatis,et al.  Early and late periodic patterns of even skipped expression are controlled by distinct regulatory elements that respond to different spatial cues , 1989, Cell.

[68]  M. Levine,et al.  Evolving enhancer-promoter interactions within the tinman complex of the flour beetle, Tribolium castaneum , 2009, Development.

[69]  A. Caplan,et al.  Irreversible gene repression model for control of development. , 1978, Science.

[70]  H. Bellen,et al.  Ten Years of Enhancer Detection: Lessons from the Fly , 1999, Plant Cell.

[71]  M. Levine,et al.  Threshold responses to the dorsal regulatory gradient and the subdivision of primary tissue territories in the Drosophila embryo. , 1996, Current opinion in genetics & development.

[72]  Esther Bae,et al.  The Abdominal-B Promoter Tethering Element Mediates Promoter-Enhancer Specificity at the Drosophila Bithorax Complex , 2007, Fly.

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

[74]  S. Small,et al.  Anterior repression of a Drosophila stripe enhancer requires three position-specific mechanisms. , 2002, Development.

[75]  A. Visel,et al.  ChIP-seq accurately predicts tissue-specific activity of enhancers , 2009, Nature.