A drosophila protein that imparts directionality on a chromatin insulator is an enhancer of position-effect variegation

The suppressor of Hairy wing (su(Hw)) protein inhibits the function of transcriptional enhancers located distally from the promoter with respect to the location of su(Hw)-binding sites. This polarity is due to the ability of the su(Hw)-binding region to form a chromatin insulator. Mutations in modifier of mdg4 (mod(mdg4)) enhance the effect of su(Hw) by inhibiting the function of enhancers located on both sides of the su(Hw)-binding region. This inhibition results in a variegated expression pattern, and mutations in mod(mdg4) act as classical enhancers of position-effect variegation. The mod(mdg4) and su(Hw) proteins interact with each other. The mod(mdg4) protein controls the nature of the repressive effect of su(Hw): in the absence of mod(mdg4) protein, su(Hw) exerts a bidirectional silencing effect, whereas in the presence of mod(mdg4), the silencing effect is transformed into unidirectional repression.

[1]  G. Felsenfeld,et al.  A 5′ element of the chicken β-globin domain serves as an insulator in human erythroid cells and protects against position effect in Drosophila , 1993, Cell.

[2]  Ira Herskowitz,et al.  A regulatory hierarchy for cell specialization in yeast , 1989, Nature.

[3]  R. Tjian,et al.  Characterization of drosophila transcription factors that activate the tandem promoters of the alcohol dehydrogenase gene , 1985, Cell.

[4]  H. Saumweber,et al.  The enhancer of position-effect variegation of Drosophila, E(var)3-93D, codes for a chromatin protein containing a conserved domain common to several transcriptional regulators. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[5]  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.

[6]  J. Rine,et al.  Silencers, silencing, and heritable transcriptional states. , 1992, Microbiological reviews.

[7]  F. Sanger,et al.  DNA sequencing with chain-terminating inhibitors. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

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

[9]  V. Corces,et al.  Interactions of retrotransposons with the host genome: the case of the gypsy element of Drosophila. , 1991, Trends in genetics : TIG.

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

[11]  S. Henikoff,et al.  Position effect and related phenomena. , 1992, Current opinion in genetics & development.

[12]  V. Corces,et al.  Mutant gene phenotypes mediated by a Drosophila melanogaster retrotransposon require sequences homologous to mammalian enhancers. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[13]  A. Spradling,et al.  Identification and genetic localization of mRNAs from ovarian follicle cells of Drosophila melanogaster , 1979, Cell.

[14]  S. Parkhurst,et al.  The Drosophila melanogaster gypsy transposable element encodes putative gene products homologous to retroviral proteins. , 1986, Molecular and cellular biology.

[15]  M. Frasch,et al.  tinman and bagpipe: two homeo box genes that determine cell fates in the dorsal mesoderm of Drosophila. , 1993, Genes & development.

[16]  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.

[17]  V. Corces,et al.  Expression of an activated ras gene causes developmental abnormalities in transgenic Drosophila melanogaster. , 1988, Genes & development.

[18]  A. Baxevanis,et al.  Interactions of coiled coils in transcription factors: where is the specificity? , 1993, Current opinion in genetics & development.

[19]  R. Kelley,et al.  The Drosophila su(Hw) gene, which controls the phenotypic effect of the gypsy transposable element, encodes a putative DNA-binding protein. , 1988, Genes & development.

[20]  M. Wilcox,et al.  Developmentally regulated alternative splicing of Drosophila integrin PS2 alpha transcripts. , 1989, Cell.

[21]  S. Parkhurst,et al.  Interactions among the gypsy transposable element and the yellow and the suppressor of hairy-wing loci in Drosophila melanogaster , 1986, Molecular and cellular biology.

[22]  V. Zakian,et al.  Telomeric position effect in yeast. , 1992, Trends in cell biology.

[23]  A. Wolffe Gene Regulation: Insulating chromatin , 1994, Current Biology.

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

[25]  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.

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

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

[28]  G. Privé,et al.  The BTB domain, found primarily in zinc finger proteins, defines an evolutionarily conserved family that includes several developmentally regulated genes in Drosophila. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[29]  Y. Jan,et al.  lola encodes a putative transcription factor required for axon growth and guidance in Drosophila. , 1994, Development.

[30]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[31]  D. Smith,et al.  Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase. , 1988, Gene.

[32]  H. Towbin,et al.  Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[33]  D. Dorsett,et al.  Expression of the cut locus in the Drosophila wing margin is required for cell type specification and is regulated by a distant enhancer. , 1991, Development.

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

[35]  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.

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

[37]  W. Bender,et al.  Sequences of the gypsy transposon of Drosophila necessary for its effects on adjacent genes. , 1988, Proceedings of the National Academy of Sciences of the United States of America.