The Experts below are selected from a list of 306237 Experts worldwide ranked by ideXlab platform

Kristen M Johansen - One of the best experts on this subject based on the ideXlab platform.

Gunter Reuter - One of the best experts on this subject based on the ideXlab platform.

  • Position-Effect Variegation, Heterochromatin Formation, and Gene Silencing in Drosophila
    Cold Spring Harbor perspectives in biology, 2013
    Co-Authors: Gunter Reuter
    Abstract:

    Position-Effect variegation (PEV) results when a gene normally in euchromatin is juxtaposed with heterochromatin by rearrangement or transPosition. When heterochromatin packaging spreads across the heterochromatin/euchromatin border, it causes transcriptional silencing in a stochastic pattern. PEV is intensely studied in Drosophila using the white gene. Screens for dominant mutations that suppress or enhance white variegation have identified many conserved epigenetic factors, including the histone H3 lysine 9 methyltransferase SU(VAR)3-9. Heterochromatin protein HP1a binds H3K9me2/3 and interacts with SU(VAR)3-9, creating a core memory system. Genetic, molecular, and biochemical analysis of PEV in Drosophila has contributed many key findings concerning establishment and maintenance of heterochromatin with concomitant gene silencing.

  • Position Effect variegation and the genetic dissection of chromatin regulation in drosophila
    Seminars in Cell & Developmental Biology, 2003
    Co-Authors: Gunnar Schotta, Rainer Dorn, Anja Ebert, Gunter Reuter
    Abstract:

    In Position-Effect variegation (PEV) genes become silenced by heterochromatisation. Genetic dissection of this process has been performed by means of dominant suppressor [Su(var)] and enhancer [E(var)] mutations. Selective genetic screens allowed mass isolation of more than 380 PEV modifier mutations identifying about 150 genes. Genetic fine structure studies revealed unique dosage dependent Effects. Most of the haplo-dependent Su(var) and E(var) genes do not display triplo-dependent Effects. Several Su(var) loci with triplo-dependent opposite enhancer Effects have been identified and shown to encode heterochromatin-associated proteins. From these the evolutionary conserved histone H3 lysine 9 methyltransferase SU(VAR)3-9 plays a central role in heterochromatic gene silencing. Molecular function of most PEV modifier genes is still unknown also including genes identified with mutations displaying lethal interaction to heterochromatin. Their analysis should contribute to further understanding of processes connected with regulation of higher order chromatin structure and epigenetic programming.

  • genetic and molecular complexity of the Position Effect variegation modifier mod mdg4 in drosophila
    Genetics, 2000
    Co-Authors: Kerstin Buchner, Gunter Reuter, Veiko Krauss, Harald Saumweber, Gunnar Schotta, Peggy Roth, Rainer Dorn
    Abstract:

    mod(mdg4), also known as E(var)3-93D, is involved in a variety of processes, such as gene silencing in Position Effect variegation (PEV), the control of gypsy insulator sequences, regulation of homeotic gene expression, and programmed cell death. We have isolated a large number of mod(mdg4) cDNAs, represent- ing 21 different isoforms generated by alternative splicing. The deduced proteins are characterized by a common N terminus of 402 amino acids, including the BTB/POZ-domain. Most of the variable C termini contain a new consensus sequence, including four Positioned hydrophobic amino acids and a Cys2His2 motif. Using specific antibodies for two protein isoforms, we demonstrate different distributions of the corresponding proteins on polytene chromosomes. Mutations in the genomic region encoding exons 1-4 show enhancement of PEV and homeotic transformation and affect viability and fertility. Homeotic and PEV phenotypes are enhanced by mutations in other trx-group genes. A transgene containing the common 59 region of mod(mdg4) that is present in all splice variants known so far partially rescues the recessive lethality of mod(mdg4) mutant alleles. Our data provide evidence that the molecular and genetic complexity of mod(mdg4) is caused by a large set of individual protein isoforms with specific functions in regulating the chromatin structure of different sets of genes throughout development.

  • Position Effect variegation in drosophila depends on dose of the gene encoding the e2f transcriptional activator and cell cycle regulator
    Development, 1996
    Co-Authors: Carole Seum, Gunter Reuter, Anne Spierer, Daniel Pauli, Janos Szidonya, Pierre Spierer
    Abstract:

    A dominant mutation due to the insertion of a P-element at 93E on the third chromosome of Drosophila melanogaster enhances Position-Effect variegation. The corresponding gene was cloned by transposon tagging and the sequence of the transcript revealed that it corresponds to the gene encoding the transcriptional activator and cell cycle regulator dE2F. The transposon-tagged allele is homozygous viable, and the insertion of the transposon in an intron correlates with a strong reduction in the amount of transcript. A homozygous lethal null allele was found to behave as a strong enhancer when heterozygous. Overexpression of the gene in transgenic flies has the opposite Effect of suppressing variegation. A link is established here, and discussed, between the dose of a transcriptional activator, which controls the cell cycle, and epigenetic silencing of chromosomal domains in Drosophila.

  • the protein encoded by the drosophila Position Effect variegation suppressor gene su var 3 9 combines domains of antagonistic regulators of homeotic gene complexes
    The EMBO Journal, 1994
    Co-Authors: B Tschiersch, Rainer Dorn, Veiko Krauss, A Hofmann, G Korge, Gunter Reuter
    Abstract:

    Abstract Modifier mutations of Position-Effect variegation (PEV) represent a useful tool for a genetic and molecular dissection of genes connected with chromatin regulation in Drosophila. The Su(var)3-9 gene belongs to the group of haplo suppressor loci which manifest a triplo enhancer Effect. Mutations show a strong suppressor Effect even in the presence of PEV enhancer mutations, indicating a central role of this gene in the regulation of PEV. By molecular analysis, Su(var)3-9 could be correlated with a 2.4 kb transcript which encodes a putative protein of 635 amino acids containing a chromo domain and a region of homology to Enhancer of zeste and trithorax, two antagonistic regulators of the Antennapedia and Bithorax gene complexes, as well as to the human protein ALL-1/Hrx which is implicated in acute leukemias. This region of homology is found in all four proteins at the C-terminus. The homology of Su(var)3-9 to both negative (Polycomb and Enhancer of zeste) and positive (trithorax) regulators of the Antennapedia and Bithorax complexes also suggests similarities in the molecular processes connected with stable transmission of a determined state and the clonal propagation of heterochromatinization.

Pierre Spierer - One of the best experts on this subject based on the ideXlab platform.

  • the genomic silencing of Position Effect variegation in drosophila melanogaster interaction between the heterochromatin associated proteins su var 3 7 and hp1
    Journal of Cell Science, 2000
    Co-Authors: Marion Delattre, Anne Spierer, Chiahwa Tonka, Pierre Spierer
    Abstract:

    Position-Effect variegation results from mosaic silencing by chromosomal rearrangements juxtaposing euchromatin genes next to pericentric heterochromatin. An increase in the amounts of the heterochromatin-associated Su(var)3-7 and HP1 proteins augments silencing. Using the yeast two-hybrid protein interaction trap system, we have isolated HP1 using Su(var)3-7 as a bait. We have then delimited three binding sites on Su(var)3-7 for HP1. On HP1, the C-terminal moiety, including the chromo shadow domain, is required for interaction. In vivo, both proteins co-localise not only in heterochromatin, but also in a limited set of sites in euchromatin and at telomeres. When delocalised to the sites bound by the protein Polycomb in euchromatin, HP1 recruits Su(var)3-7. Finally, and in contrast with euchromatin genes, a decrease in the amounts of both proteins enhances variegation of the light gene, one of the few genetic loci mapped within pericentric heterochromatin. This body of data supports a direct link between Su(var)3-7 and HP1 in the genomic silencing of Position-Effect variegation.

  • su var 3 7 a drosophila heterochromatin associated protein and companion of hp1 in the genomic silencing of Position Effect variegation
    The EMBO Journal, 1997
    Co-Authors: Fabienne Cléard, Marion Delattre, Pierre Spierer
    Abstract:

    An increase in the dose of the Su(var)3-7 locus of Drosophila melanogaster enhances the genomic silencing of Position-Effect variegation caused by centromeric heterochromatin. Here we show that the product of Su(var)3-7 is a nuclear protein which associates with pericentromeric heterochromatin at interphase, whether on diploid chromosomes from embryonic nuclei or on polytene chromosomes from larval salivary glands. The protein also associates with the partially heterochromatic chromosome 4. As these phenotypes and localizations resemble those described by others for the Su(var)2-5 locus and its heterochromatin-associated protein HP1, the presumed co-operation of the two proteins was tested further. The Effect of the dose of Su(var)3-7 on silencing of a number of variegating rearrangements and insertions is strikingly similar to the Effect of the dose of Su(var)2-5 reported by others. In addition, the two loci interact genetically, and the two proteins co-immunoprecipitate from nuclear extracts. The results suggest that SU(VAR)3-7 and HP1 co-operate in building the genomic silencing associated with heterochromatin.

  • Position Effect variegation in drosophila depends on dose of the gene encoding the e2f transcriptional activator and cell cycle regulator
    Development, 1996
    Co-Authors: Carole Seum, Gunter Reuter, Anne Spierer, Daniel Pauli, Janos Szidonya, Pierre Spierer
    Abstract:

    A dominant mutation due to the insertion of a P-element at 93E on the third chromosome of Drosophila melanogaster enhances Position-Effect variegation. The corresponding gene was cloned by transposon tagging and the sequence of the transcript revealed that it corresponds to the gene encoding the transcriptional activator and cell cycle regulator dE2F. The transposon-tagged allele is homozygous viable, and the insertion of the transposon in an intron correlates with a strong reduction in the amount of transcript. A homozygous lethal null allele was found to behave as a strong enhancer when heterozygous. Overexpression of the gene in transgenic flies has the opposite Effect of suppressing variegation. A link is established here, and discussed, between the dose of a transcriptional activator, which controls the cell cycle, and epigenetic silencing of chromosomal domains in Drosophila.

Marion Delattre - One of the best experts on this subject based on the ideXlab platform.

  • jil 1 and su var 3 7 interact genetically and counteract each other s Effect on Position Effect variegation in drosophila
    Genetics, 2010
    Co-Authors: Huai Deng, Marion Delattre, Stephanie Lerach, Jack Girton, Jorgen Johansen, Chao Wang, Weili Cai, Kristen M Johansen
    Abstract:

    The essential JIL-1 histone H3S10 kinase is a key regulator of chromatin structure that functions to maintain euchromatic domains while counteracting heterochromatization and gene silencing. In the absence of the JIL-1 kinase, two of the major heterochromatin markers H3K9me2 and HP1a spread in tandem to ectopic locations on the chromosome arms. Here we address the role of the third major heterochromatin component, the zinc-finger protein Su(var)3-7. We show that the lethality but not the chromosome morphology defects associated with the null JIL-1 phenotype to a large degree can be rescued by reducing the dose of the Su(var)3-7 gene and that Su(var)3-7 and JIL-1 loss-of-function mutations have an antagonistic and counterbalancing Effect on Position-Effect variegation (PEV). Furthermore, we show that in the absence of JIL-1 kinase activity, Su(var)3-7 gets redistributed and upregulated on the chromosome arms. Reducing the dose of the Su(var)3-7 gene dramatically decreases this redistribution; however, the spreading of H3K9me2 to the chromosome arms was unaffected, strongly indicating that ectopic Su(var)3-9 activity is not a direct cause of lethality. These observations suggest a model where Su(var)3-7 functions as an Effector downstream of Su(var)3-9 and H3K9 dimethylation in heterochromatic spreading and gene silencing that is normally counteracted by JIL-1 kinase activity.

  • the genomic silencing of Position Effect variegation in drosophila melanogaster interaction between the heterochromatin associated proteins su var 3 7 and hp1
    Journal of Cell Science, 2000
    Co-Authors: Marion Delattre, Anne Spierer, Chiahwa Tonka, Pierre Spierer
    Abstract:

    Position-Effect variegation results from mosaic silencing by chromosomal rearrangements juxtaposing euchromatin genes next to pericentric heterochromatin. An increase in the amounts of the heterochromatin-associated Su(var)3-7 and HP1 proteins augments silencing. Using the yeast two-hybrid protein interaction trap system, we have isolated HP1 using Su(var)3-7 as a bait. We have then delimited three binding sites on Su(var)3-7 for HP1. On HP1, the C-terminal moiety, including the chromo shadow domain, is required for interaction. In vivo, both proteins co-localise not only in heterochromatin, but also in a limited set of sites in euchromatin and at telomeres. When delocalised to the sites bound by the protein Polycomb in euchromatin, HP1 recruits Su(var)3-7. Finally, and in contrast with euchromatin genes, a decrease in the amounts of both proteins enhances variegation of the light gene, one of the few genetic loci mapped within pericentric heterochromatin. This body of data supports a direct link between Su(var)3-7 and HP1 in the genomic silencing of Position-Effect variegation.

  • su var 3 7 a drosophila heterochromatin associated protein and companion of hp1 in the genomic silencing of Position Effect variegation
    The EMBO Journal, 1997
    Co-Authors: Fabienne Cléard, Marion Delattre, Pierre Spierer
    Abstract:

    An increase in the dose of the Su(var)3-7 locus of Drosophila melanogaster enhances the genomic silencing of Position-Effect variegation caused by centromeric heterochromatin. Here we show that the product of Su(var)3-7 is a nuclear protein which associates with pericentromeric heterochromatin at interphase, whether on diploid chromosomes from embryonic nuclei or on polytene chromosomes from larval salivary glands. The protein also associates with the partially heterochromatic chromosome 4. As these phenotypes and localizations resemble those described by others for the Su(var)2-5 locus and its heterochromatin-associated protein HP1, the presumed co-operation of the two proteins was tested further. The Effect of the dose of Su(var)3-7 on silencing of a number of variegating rearrangements and insertions is strikingly similar to the Effect of the dose of Su(var)2-5 reported by others. In addition, the two loci interact genetically, and the two proteins co-immunoprecipitate from nuclear extracts. The results suggest that SU(VAR)3-7 and HP1 co-operate in building the genomic silencing associated with heterochromatin.

Huai Deng - One of the best experts on this subject based on the ideXlab platform.

  • regulation of Position Effect variegation at pericentric heterochromatin by drosophila keap1 nrf2 xenobiotic response factors
    Genesis, 2019
    Co-Authors: Jennifer H Carlson, Thane Swisse, Charles E Smith, Huai Deng
    Abstract:

    The Keap1-Nrf2 signaling pathway plays a central role in the regulation of transcriptional responses to oxidative species and xenobiotic stimuli. The complete range of molecular mechanisms and biological functions of Keap1 and Nrf2 remain to be fully elucidated. To determine the potential roles of Keap1 and Nrf2 in chromatin architecture, we examined the Effects of their Drosophila homologs (dKeap1 and CncC) on Position Effect variegation (PEV), which is a transcriptional reporter for heterochromatin formation and spreading. Loss of function mutations in cncC, dKeap1, and cncC/dKeap1 double mutants all suppressed the variegation of wm4 and SbV PEV alleles, indicating that reduction of CncC or dKeap1 causes a decrease of heterochromatic silencing at pericentric region. Depletion of CncC or dKeap1 in embryos reduced the level of the H3K9me2 heterochromatin marker, but had no Effect on the transcription of the genes encoding Su(var)3-9 and HP1. These results support a potential role of dKeap1 and CncC in the establishment and/or maintenance of pericentric heterochromatin. Our study provides preliminary evidence for a novel epigenetic function of Keap1-Nrf2 oxidative/xenobiotic response factors in chromatin remodeling.

  • jil 1 and su var 3 7 interact genetically and counteract each other s Effect on Position Effect variegation in drosophila
    Genetics, 2010
    Co-Authors: Huai Deng, Marion Delattre, Stephanie Lerach, Jack Girton, Jorgen Johansen, Chao Wang, Weili Cai, Kristen M Johansen
    Abstract:

    The essential JIL-1 histone H3S10 kinase is a key regulator of chromatin structure that functions to maintain euchromatic domains while counteracting heterochromatization and gene silencing. In the absence of the JIL-1 kinase, two of the major heterochromatin markers H3K9me2 and HP1a spread in tandem to ectopic locations on the chromosome arms. Here we address the role of the third major heterochromatin component, the zinc-finger protein Su(var)3-7. We show that the lethality but not the chromosome morphology defects associated with the null JIL-1 phenotype to a large degree can be rescued by reducing the dose of the Su(var)3-7 gene and that Su(var)3-7 and JIL-1 loss-of-function mutations have an antagonistic and counterbalancing Effect on Position-Effect variegation (PEV). Furthermore, we show that in the absence of JIL-1 kinase activity, Su(var)3-7 gets redistributed and upregulated on the chromosome arms. Reducing the dose of the Su(var)3-7 gene dramatically decreases this redistribution; however, the spreading of H3K9me2 to the chromosome arms was unaffected, strongly indicating that ectopic Su(var)3-9 activity is not a direct cause of lethality. These observations suggest a model where Su(var)3-7 functions as an Effector downstream of Su(var)3-9 and H3K9 dimethylation in heterochromatic spreading and gene silencing that is normally counteracted by JIL-1 kinase activity.

  • loss of function alleles of the jil 1 histone h3s10 kinase enhance Position Effect variegation at pericentric sites in drosophila heterochromatin
    Genetics, 2007
    Co-Authors: Xiaomin Bao, Huai Deng, Jack Girton, Jorgen Johansen, Kristen M Johansen
    Abstract:

    In this study we show that loss-of-function alleles of the JIL-1 histone H3S10 kinase act as enhancers of Position-Effect variegation at pericentric sites whereas the gain-of-function JIL-1Su(var)3-1[3] allele acts as a suppressor strongly supporting a functional role for JIL-1 in maintaining euchromatic chromatin and counteracting heterochromatic spreading and gene silencing.

  • loss of function alleles of the jil 1 kinase are strong suppressors of Position Effect variegation of the wm4 allele in drosophila
    Genetics, 2006
    Co-Authors: Stephanie Lerach, Weiguo Zhang, Xiaomin Bao, Huai Deng, Jack Girton, Jorgen Johansen, Kristen M Johansen
    Abstract:

    In this article we show that hypomorphic loss-of-function alleles of the JIL-1 histone H3S10 kinase are strong suppressors of Position Effect variegation (PEV) of the wm4 allele and that lack of JIL-1 activity can counteract the Effect of the dominant enhancer E(var)2-1 on PEV.