An endogenous Su(Hw) insulator separates the yellow gene from the Achaete-scute gene complex in Drosophila

The best characterized chromatin insulator in Drosophila is the Suppressor of Hairy wing binding region contained within the gypsy retrotransposon. Although cellular functions have been suggested, no role has been found yet for the multitude of endogenous Suppressor of Hairy wing binding sites. Here we show that two Suppressor of Hairy wing binding sites in the intergenic region between the yellow gene and the Achaete-scute gene complex form a functional insulator. Genetic analysis shows that at least two proteins, Suppressor of Hairy wing and Modifier of MDG4, required for the activity of this insulator, are involved in the transcriptional regulation of Achaete-scute.

[1]  V. Corces,et al.  The suppressor of Hairy-wing binding region is required for gypsy mutagenesis , 1992, Molecular and General Genetics MGG.

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

[3]  Ricardo Villares,et al.  Molecular genetics of the achaete-scute gene complex of D. melanogaster , 1985, Cell.

[4]  G. Rubin,et al.  Transposition of cloned P elements into Drosophila germ line chromosomes. , 1982, Science.

[5]  D. Dorsett,et al.  Distant liaisons: long-range enhancer-promoter interactions in Drosophila. , 1999, Current opinion in genetics & development.

[6]  V. Corces,et al.  Separate regulatory elements are responsible for the complex pattern of tissue-specific and developmental transcription of the yellow locus in Drosophila melanogaster. , 1987, Genes & development.

[7]  V. Corces,et al.  A leucine zipper domain of the suppressor of Hairy-wing protein mediates its repressive effect on enhancer function. , 1993, Genes & development.

[8]  M. Levine,et al.  The gypsy insulator can function as a promoter‐specific silencer in the Drosophila embryo , 1997, The EMBO journal.

[9]  F. Karch,et al.  The Fab-8 boundary defines the distal limit of the bithorax complex iab-7 domain and insulates iab-7 from initiation elements and a PRE in the adjacent iab-8 domain. , 2000, Development.

[10]  A. West,et al.  Insulators: many functions, many mechanisms. , 2002, Genes & development.

[11]  J. Lechner A zinc finger protein , 1994 .

[12]  G. Schotta,et al.  Genetic and molecular complexity of the position effect variegation modifier mod(mdg4) in Drosophila. , 2000, Genetics.

[13]  V. Pirrotta,et al.  The su(Hw) protein insulates expression of the Drosophila melanogaster white gene from chromosomal position‐effects. , 1993, The EMBO journal.

[14]  M. Levine,et al.  Modulation of enhancer-promoter interactions by insulators in the Drosophila embryo. , 1995, Nature.

[15]  P. Georgiev,et al.  The su(Hw) Insulator Can Disrupt Enhancer-Promoter Interactions When Located More than 20 Kilobases Away from the Drosophila achaete-scute Complex , 1999, Molecular and Cellular Biology.

[16]  J. Modolell,et al.  Cis-regulation of achaete and scute: shared enhancer-like elements drive their coexpression in proneural clusters of the imaginal discs. , 1995, Genes & development.

[17]  J. Modolell,et al.  Molecular analysis of the asense gene, a member of the achaete‐scute complex of Drosophila melanogaster, and its novel role in optic lobe development. , 1989, The EMBO journal.

[18]  H. Smith,et al.  Genetic transformation. , 1981, Annual review of biochemistry.

[19]  W. Chia,et al.  Regulatory elements involved in the tissue-specific expression of the yellow gene of Drosophila , 1989, Molecular and General Genetics MGG.

[20]  J. Modolell,et al.  Deletion analysis of the achaete-scute locus of Drosophila melanogaster. , 1987, Genes & development.

[21]  D. Lindsley,et al.  The Genome of Drosophila Melanogaster , 1992 .

[22]  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.

[23]  R. Khesin,et al.  Molecular Genetics , 1968, Springer Berlin Heidelberg.

[24]  V. Corces,et al.  DNA bending is a determinant of binding specificity for a Drosophila zinc finger protein. , 1990, Genes & development.

[25]  R. Nagoshi,et al.  A P element containing suppressor of hairy-wing binding regions has novel properties for mutagenesis in Drosophila melanogaster. , 1995, Genetics.

[26]  D. Dorsett,et al.  The DNA-binding and enhancer-blocking domains of the Drosophila suppressor of Hairy-wing protein , 1996, Molecular and cellular biology.

[27]  C. Sigrist,et al.  Chromatin insulator elements block the silencing of a target gene by the Drosophila polycomb response element (PRE) but allow trans interactions between PREs on different chromosomes. , 1997, Genetics.

[28]  A. Mazo,et al.  Suppression in Drosophila: su(Hw) and su(f) gene products interact with a region of gypsy (mdg4) regulating its transcriptional activity. , 1989, The EMBO journal.

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

[30]  V. Corces,et al.  The Drosophila melanogaster suppressor of Hairy-wing protein binds to specific sequences of the gypsy retrotransposon. , 1988, Genes & development.

[31]  V. Corces,et al.  Characterization of functional domains of the su(Hw) protein that mediate the silencing effect of mod(mdg4) mutations. , 1997, Genetics.

[32]  D. Hartl,et al.  Application of Cre/loxP in Drosophila. Site-specific recombination and transgene coplacement. , 2000, Methods in molecular biology.

[33]  D. Dorsett Potentiation of a polyadenylylation site by a downstream protein-DNA interaction. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[34]  C. Burks,et al.  Characterization of the transvection mediating region of the abdominal-B locus in Drosophila. , 1999, Development.

[35]  M. Bate,et al.  Lethal of scute, a proneural gene, participates in the specification of muscle progenitors during Drosophila embryogenesis. , 1995, Genes & development.

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

[37]  D. Dorsett,et al.  Repression of hsp70 heat shock gene transcription by the suppressor of hairy-wing protein of Drosophila melanogaster , 1991, Molecular and cellular biology.

[38]  V. Corces,et al.  Setting the Boundaries of Chromatin Domains and Nuclear Organization , 2002, Cell.

[39]  P. Georgiev,et al.  Interaction between mutations in the suppressor of Hairy wing and modifier of mdg4 genes of Drosophila melanogaster affecting the phenotype of gypsy-induced mutations. , 1996, Genetics.

[40]  P. Georgiev,et al.  Novel genes influencing the expression of the yellow locus and mdg4 (gypsy) in Drosophila melanogaster , 1989, Molecular and General Genetics MGG.

[41]  H. Hovhannisyan,et al.  hobo Induced rearrangements in the yellow locus influence the insulation effect of the gypsy su(Hw)-binding region in Drosophila melanogaster. , 1998, Genetics.

[42]  J. Modolell,et al.  The achaete-scute complex as an integrating device. , 1998, The International journal of developmental biology.

[43]  P. Geyer,et al.  Polycomb group repression is blocked by the Drosophila suppressor of Hairy-wing [su(Hw)] insulator. , 1998, Genetics.

[44]  V. Pirrotta,et al.  Molecular analysis of the zeste-white interaction reveals a promoter-proximal element essential for distant enhancer-promoter communication. , 1992, Genetics.

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

[46]  G. Rubin,et al.  Analysis of P transposable element functions in drosophila , 1984, Cell.

[47]  V. Corces,et al.  Dominant effects of suppressor of Hairy-wing mutations on gypsy-induced alleles of forked and cut in Drosophila melanogaster. , 1992, Genetics.

[48]  S. Lindquist,et al.  The FLP recombinase of yeast catalyzes site-specific recombination in the drosophila genome , 1989, Cell.

[49]  P. Geyer,et al.  Enhancer blocking by the Drosophila gypsy insulator depends upon insulator anatomy and enhancer strength. , 1999, Genetics.

[50]  V. Pirrotta,et al.  Loss of insulator activity by paired Su(Hw) chromatin insulators. , 2001, Science.

[51]  V. Corces,et al.  On the molecular mechanism of gypsy‐induced mutations at the yellow locus of Drosophila melanogaster. , 1986, The EMBO journal.

[52]  A. West,et al.  Insulators and boundaries: versatile regulatory elements in the eukaryotic genome. , 2001, Science.

[53]  D. Dorsett,et al.  Insulation of Enhancer-Promoter Communication by a Gypsy Transposon Insert in the Drosophila cut Gene: Cooperation between Suppressor of Hairy-wing and Modifier of mdg4 Proteins , 2001, Molecular and Cellular Biology.

[54]  V. Corces,et al.  Two insulators are not better than one , 2001, Nature Structural Biology.

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

[56]  G. Rubin,et al.  Genetic transformation of Drosophila with transposable element vectors. , 1982, Science.

[57]  P. Shen,et al.  Effects of cis arrangement of chromatin insulators on enhancer-blocking activity. , 2001, Science.

[58]  V. Corces,et al.  Interactions between the Su(Hw) and Mod(mdg4) proteins required for gypsy insulator function , 2001, The EMBO journal.

[59]  A. Udvardy Dividing the empire: boundary chromatin elements delimit the territory of enhancers , 1999, The EMBO journal.

[60]  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.

[61]  P. Schedl,et al.  Chromatin domain boundaries in the Bithorax complex , 1998, Cellular and Molecular Life Sciences CMLS.

[62]  J. Modolell,et al.  Xiro, a Xenopus homolog of the Drosophila Iroquois complex genes, controls development at the neural plate , 1998, The EMBO journal.

[63]  V. Corces,et al.  Chromatin insulators and boundaries: effects on transcription and nuclear organization. , 2001, Annual review of genetics.

[64]  V. Corces,et al.  A chromatin insulator determines the nuclear localization of DNA. , 2000, Molecular cell.