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Eliette Bonnefoy - One of the best experts on this subject based on the ideXlab platform.

  • A SAP30 complex inhibits IFN-beta expression in Rift Valley fever virus infected cells.
    PLoS pathogens, 2008
    Co-Authors: Nicolas Le May, Zeyni Mansuroglu, Psylvia Leger, Thibaut Josse, Guillaume Blot, Agnès Billecocq, Ramon Flick, Yves Jacob, Michèle Bouloy, Eliette Bonnefoy
    Abstract:

    Rift Valley fever virus (RVFV) nonstructural protein NSs acts as the major determinant of virulence by antagonizing interferon β (IFN-β) gene expression. We demonstrate here that NSs interacts with the host protein SAP30, which belongs to Sin3A/NCoR/HDACs repressor complexes and interacts with the Transcription Factor YY1 that regulates IFN-β gene expression. Using confocal microscopy and chromatin immunoprecipitation, we show that SAP30, YY1, and Sin3A-associated corepressor Factors strongly colocalize with nuclear NSs filaments and that NSs, SAP30 and Sin3A-associated Factors are recruited on the IFN-β promoter through YY1, inhibiting CBP recruitment, histone acetylation, and Transcriptional activation. To ascertain the role of SAP30, we produced, by reverse genetics, a recombinant RVFV in which the interacting domain in NSs was deleted. The virus was unable to inhibit the IFN response and was avirulent for mice. We discuss here the strategy developed by the highly pathogenic RVFV to evade the host antiviral response, affecting nuclear organization and IFN-β promoter chromatin structure.

  • A SAP30 complex inhibits IFN-beta expression in Rift Valley fever virus infected cells.
    PLoS Pathogens, 2008
    Co-Authors: Nicolas Le May, Zeyni Mansuroglu, Eliette Bonnefoy, Psylvia Leger, Thibaut Josse, Guillaume Blot, Agnès Billecocq, Ramon Flick, Yves Jacob, Michèle Bouloy
    Abstract:

    Rift Valley fever virus (RVFV) nonstructural protein NSs acts as the major determinant of virulence by antagonizing interferon beta (IFN-beta) gene expression. We demonstrate here that NSs interacts with the host protein SAP30, which belongs to Sin3A/NCoR/HDACs repressor complexes and interacts with the Transcription Factor YY1 that regulates IFN-beta gene expression. Using confocal microscopy and chromatin immunoprecipitation, we show that SAP30, YY1, and Sin3A-associated corepressor Factors strongly colocalize with nuclear NSs filaments and that NSs, SAP30 and Sin3A-associated Factors are recruited on the IFN-beta promoter through YY1, inhibiting CBP recruitment, histone acetylation, and Transcriptional activation. To ascertain the role of SAP30, we produced, by reverse genetics, a recombinant RVFV in which the interacting domain in NSs was deleted. The virus was unable to inhibit the IFN response and was avirulent for mice. We discuss here the strategy developed by the highly pathogenic RVFV to evade the host antiviral response, affecting nuclear organization and IFN-beta promoter chromatin structure.

  • Transcription Factor YY1 associates with pericentromeric γ-satellite DNA in cycling but not in quiescent (G0) cells
    Nucleic acids research, 2004
    Co-Authors: Elena A Shestakova, Zeyni Mansuroglu, Houda Mokrani, Nicolae Ghinea, Eliette Bonnefoy
    Abstract:

    Pericentromeric gamma-satellite DNA is organized in constitutive heterochromatin structures. It comprises a 234 bp sequence repeated several thousands times surrounding the centromeric sequence of all murine chromosomes. Potential binding sites for Transcription Factor Yin Yang 1 (YY1), a repressor or activator of several cellular and viral genes, are present in pericentromeric gamma-satellite DNA. Using gel retardation and chromatin immunoprecipitation, we demonstrate in this work that YY1 specifically interacts in vitro and in vivo with gamma-satellite DNA. Using immunoFISH and confocal microscopy we show that YY1 specifically co-localizes with pericentromeric gamma-satellite DNA clusters organized in constitutive heterochromatin in murine L929 and 3T3 fibroblasts cell lines. Immunoelectron microscopy experiments further confirmed YY1 localization in heterochromatic areas. Overall, our results demonstrate for the first time that a fraction of YY1 is directly associated with constitutive heterochromatin structures. This association appears physiologically relevant since the association of YY1 with pericentromeric gamma-satellite DNA observed in cycling 3T3 fibroblasts strongly diminished in quiescent (G0) 3T3 fibroblasts. We discuss the implications of these results in the context of heterochromatin formation as well as with regard to the YY1-induced repression of euchromatic genes.

  • Transcription Factor YY1 associates with pericentromeric gamma-satellite DNA in cycling but not in quiescent (G0) cells.
    Nucleic Acids Research, 2004
    Co-Authors: Elena A Shestakova, Zeyni Mansuroglu, Houda Mokrani, Nicolae Ghinea, Eliette Bonnefoy
    Abstract:

    Pericentromeric gamma-satellite DNA is organized in constitutive heterochromatin structures. It comprises a 234 bp sequence repeated several thousands times surrounding the centromeric sequence of all murine chromosomes. Potential binding sites for Transcription Factor Yin Yang 1 (YY1), a repressor or activator of several cellular and viral genes, are present in pericentromeric gamma-satellite DNA. Using gel retardation and chromatin immunoprecipitation, we demonstrate in this work that YY1 specifically interacts in vitro and in vivo with gamma-satellite DNA. Using immunoFISH and confocal microscopy we show that YY1 specifically co-localizes with pericentromeric gamma-satellite DNA clusters organized in constitutive heterochromatin in murine L929 and 3T3 fibroblasts cell lines. Immunoelectron microscopy experiments further confirmed YY1 localization in heterochromatic areas. Overall, our results demonstrate for the first time that a fraction of YY1 is directly associated with constitutive heterochromatin structures. This association appears physiologically relevant since the association of YY1 with pericentromeric gamma-satellite DNA observed in cycling 3T3 fibroblasts strongly diminished in quiescent (G0) 3T3 fibroblasts. We discuss the implications of these results in the context of heterochromatin formation as well as with regard to the YY1-induced repression of euchromatic genes.

  • Transcription Factor YY1 Binds to the Murine Beta Interferon Promoter and Regulates Its Transcriptional Capacity with a Dual Activator/Repressor Role
    Journal of virology, 2003
    Co-Authors: Laure Weill, Elena A Shestakova, Eliette Bonnefoy
    Abstract:

    The induction of the beta interferon (IFN-beta) gene constitutes one of the first responses of the cell to virus infection. Its regulation is achieved through an intricate combination of virus-induced binding of Transcription Factors and local chromatin remodeling. In this work, we demonstrate that Transcription Factor YY1, known to interact with histone deacetylases (HDAC) and histone acetyltransferases, has a dual activator/repressor role during the regulation of the IFN-beta promoter activity. We show that YY1 specifically binds in vitro and in vivo to the murine IFN-beta promoter at positions -90 and -122. Overexpression of YY1 strongly repressed the Transcriptional capacity of a stably integrated IFN-beta promoter fused to a chloramphenicol acetyltransferase reporter gene as well as the endogenous IFN activity of murine L929 cells via an HDAC activity. Stably integrated IFN-beta promoters mutated at the -90 site were no longer repressed by YY1, could no longer be activated by trichostatin A, displayed a retarded postinduction turn off, and a reduced virus-induced activity. Introduction of a mutation at the -122 site did not affect YY1-induced repression, but promoters with this mutation displayed a reduced virus-induced activity. Stably integrated full-length promoters (from position -330 to +20) mutated at both YY1-binding sites displayed extremely reduced promoter activities. We conclude that YY1 has a dual activator/repressor role on IFN-beta promoter activity depending on its binding site and time after infection.

Edward Seto - One of the best experts on this subject based on the ideXlab platform.

  • targeted recruitment of a histone h4 specific methyltransferase by the Transcription Factor YY1
    Genes & Development, 2003
    Co-Authors: Natalie Rezaizadeh, Ya-li Yao, Xiaohong Zhang, Fares Namour, Gyorgy Fejer, Yuder Wen, Ildiko Gyory, Kenneth L Wright, Edward Seto
    Abstract:

    Methylation of specific residues within the N-terminal histone tails plays a critical role in regulating eukaryotic gene expression. Although great advances have been made toward identifying histone methyltransferases (HMTs) and elucidating the consequences of histone methylation, little is known about the recruitment of HMTs to regulatory regions of chromatin. Here we report that the sequence-specific DNA-binding Transcription Factor Yin Yang 1 (YY1) binds to and recruits the histone H4 (Arg 3)-specific methyltransferase, PRMT1, to a YY1-activated promoter. Our data confirm that histone methylation does not occur randomly but rather is a targeted event and provides one mechanism by which HMTs can be recruited to chromatin to activate gene expression.

  • The FK506‐binding protein 25 functionally associates with histone deacetylases and with Transcription Factor YY1
    The EMBO journal, 2001
    Co-Authors: Wen-ming Yang, Ya-li Yao, Edward Seto
    Abstract:

    FK506-binding proteins (FKBPs) are cellular receptors for immunosuppressants that belong to a subgroup of proteins, known as immunophilins, with peptidylprolyl cis–trans isomerase (PPIase) activity. Sequence comparison suggested that the HD2-type histone deacetylases and the FKBP-type PPIases may have evolved from a common ancestor enzyme. Here we show that FKBP25 physically associates with the histone deacetylases HDAC1 and HDAC2 and with the HDAC-binding Transcriptional regulator YY1. An FKBP25 immunoprecipitated complex contains deacetylase activity, and this activity is associated with the N-terminus of FKBP25, distinct from the FK506/rapamycin-binding domain. Furthermore, FKBP25 can alter the DNA-binding activity of YY1. Together, our data firmly establish a relationship between histone deacetylases and the FKBP enzymes and provide a novel and critical function for the FKBPs.

  • the fk506 binding protein 25 functionally associates with histone deacetylases and with Transcription Factor YY1
    The EMBO Journal, 2001
    Co-Authors: Wen-ming Yang, Ya-li Yao, Edward Seto
    Abstract:

    FK506-binding proteins (FKBPs) are cellular receptors for immunosuppressants that belong to a subgroup of proteins, known as immunophilins, with peptidylprolyl cis–trans isomerase (PPIase) activity. Sequence comparison suggested that the HD2-type histone deacetylases and the FKBP-type PPIases may have evolved from a common ancestor enzyme. Here we show that FKBP25 physically associates with the histone deacetylases HDAC1 and HDAC2 and with the HDAC-binding Transcriptional regulator YY1. An FKBP25 immunoprecipitated complex contains deacetylase activity, and this activity is associated with the N-terminus of FKBP25, distinct from the FK506/rapamycin-binding domain. Furthermore, FKBP25 can alter the DNA-binding activity of YY1. Together, our data firmly establish a relationship between histone deacetylases and the FKBP enzymes and provide a novel and critical function for the FKBPs.

  • Regulation of Transcription Factor YY1 by Acetylation and Deacetylation
    Molecular and cellular biology, 2001
    Co-Authors: Ya-li Yao, Wen-ming Yang, Edward Seto
    Abstract:

    YY1 is a sequence-specific DNA-binding Transcription Factor that has many important biological roles. It activates or represses many genes during cell growth and differentiation and is also required for the normal development of mammalian embryos. Previous studies have established that YY1 interacts with histone acetyltransferases p300 and CREB-binding protein (CBP) and histone deacetylase 1 (HDAC1), HDAC2, and HDAC3. Here, we present evidence that the activity of YY1 is regulated through acetylation by p300 and PCAF and through deacetylation by HDACs. YY1 was acetylated in two regions: both p300 and PCAF acetylated the central glycine-lysine-rich domain of residues 170 to 200, and PCAF also acetylated YY1 at the C-terminal DNA-binding zinc finger domain. Acetylation of the central region was required for the full Transcriptional repressor activity of YY1 and targeted YY1 for active deacetylation by HDACs. However, the C-terminal region of YY1 could not be deacetylated. Rather, the acetylated C-terminal region interacted with HDACs, which resulted in stable HDAC activity associated with the YY1 protein. Finally, acetylation of the C-terminal zinc finger domain decreased the DNA-binding activity of YY1. Our findings suggest that in the natural context, YY1 activity is regulated through intricate mechanisms involving negative feedback loops, histone deacetylation, and recognition of the cognate DNA sequence affected by acetylation and deacetylation of the YY1 protein.

  • unlocking the mechanisms of Transcription Factor YY1 are chromatin modifying enzymes the key
    Gene, 1999
    Co-Authors: Matthew J Thomas, Edward Seto
    Abstract:

    The Transcription Factor YY1 is a complex protein that is involved in repressing and activating a diverse number of promoters. Numerous studies have attempted to understand how this one Factor can act both as a repressor and an activator in such a wide set of different contexts. The fact that YY1 interacts with a number of key regulatory proteins (e.g. TBP, TFIIB, TAFII55, Sp1, and E1A) has suggested that these interactions are important for determining which particular function of YY1 is displayed at a specific promoter. Two groups of proteins, previously known to function as corepressors and coactivators, that now seem likely to modulate YY1's functions, are the histone deacetylases (HDAC) and histone acetyltransferases (HAT). These two groups of enzymes modify histones, and this modification is proposed to alter chromatin structure. Acetylated histones are typically localized to active chromatin while deacetylated histones colocalize with Transcriptionally inactive chromatin. When these enzymes are directed to a promoter through a DNA binding Factor such as YY1, that promoter can be activated or repressed. This review will discuss the recent work dealing with the different proteins that interact with YY1, with particular emphasis on ones that modify chromatin, and how they could be involved in regulating YY1's activities.

Zeyni Mansuroglu - One of the best experts on this subject based on the ideXlab platform.

  • A SAP30 complex inhibits IFN-beta expression in Rift Valley fever virus infected cells.
    PLoS pathogens, 2008
    Co-Authors: Nicolas Le May, Zeyni Mansuroglu, Psylvia Leger, Thibaut Josse, Guillaume Blot, Agnès Billecocq, Ramon Flick, Yves Jacob, Michèle Bouloy, Eliette Bonnefoy
    Abstract:

    Rift Valley fever virus (RVFV) nonstructural protein NSs acts as the major determinant of virulence by antagonizing interferon β (IFN-β) gene expression. We demonstrate here that NSs interacts with the host protein SAP30, which belongs to Sin3A/NCoR/HDACs repressor complexes and interacts with the Transcription Factor YY1 that regulates IFN-β gene expression. Using confocal microscopy and chromatin immunoprecipitation, we show that SAP30, YY1, and Sin3A-associated corepressor Factors strongly colocalize with nuclear NSs filaments and that NSs, SAP30 and Sin3A-associated Factors are recruited on the IFN-β promoter through YY1, inhibiting CBP recruitment, histone acetylation, and Transcriptional activation. To ascertain the role of SAP30, we produced, by reverse genetics, a recombinant RVFV in which the interacting domain in NSs was deleted. The virus was unable to inhibit the IFN response and was avirulent for mice. We discuss here the strategy developed by the highly pathogenic RVFV to evade the host antiviral response, affecting nuclear organization and IFN-β promoter chromatin structure.

  • A SAP30 complex inhibits IFN-beta expression in Rift Valley fever virus infected cells.
    PLoS Pathogens, 2008
    Co-Authors: Nicolas Le May, Zeyni Mansuroglu, Eliette Bonnefoy, Psylvia Leger, Thibaut Josse, Guillaume Blot, Agnès Billecocq, Ramon Flick, Yves Jacob, Michèle Bouloy
    Abstract:

    Rift Valley fever virus (RVFV) nonstructural protein NSs acts as the major determinant of virulence by antagonizing interferon beta (IFN-beta) gene expression. We demonstrate here that NSs interacts with the host protein SAP30, which belongs to Sin3A/NCoR/HDACs repressor complexes and interacts with the Transcription Factor YY1 that regulates IFN-beta gene expression. Using confocal microscopy and chromatin immunoprecipitation, we show that SAP30, YY1, and Sin3A-associated corepressor Factors strongly colocalize with nuclear NSs filaments and that NSs, SAP30 and Sin3A-associated Factors are recruited on the IFN-beta promoter through YY1, inhibiting CBP recruitment, histone acetylation, and Transcriptional activation. To ascertain the role of SAP30, we produced, by reverse genetics, a recombinant RVFV in which the interacting domain in NSs was deleted. The virus was unable to inhibit the IFN response and was avirulent for mice. We discuss here the strategy developed by the highly pathogenic RVFV to evade the host antiviral response, affecting nuclear organization and IFN-beta promoter chromatin structure.

  • Transcription Factor YY1 associates with pericentromeric γ-satellite DNA in cycling but not in quiescent (G0) cells
    Nucleic acids research, 2004
    Co-Authors: Elena A Shestakova, Zeyni Mansuroglu, Houda Mokrani, Nicolae Ghinea, Eliette Bonnefoy
    Abstract:

    Pericentromeric gamma-satellite DNA is organized in constitutive heterochromatin structures. It comprises a 234 bp sequence repeated several thousands times surrounding the centromeric sequence of all murine chromosomes. Potential binding sites for Transcription Factor Yin Yang 1 (YY1), a repressor or activator of several cellular and viral genes, are present in pericentromeric gamma-satellite DNA. Using gel retardation and chromatin immunoprecipitation, we demonstrate in this work that YY1 specifically interacts in vitro and in vivo with gamma-satellite DNA. Using immunoFISH and confocal microscopy we show that YY1 specifically co-localizes with pericentromeric gamma-satellite DNA clusters organized in constitutive heterochromatin in murine L929 and 3T3 fibroblasts cell lines. Immunoelectron microscopy experiments further confirmed YY1 localization in heterochromatic areas. Overall, our results demonstrate for the first time that a fraction of YY1 is directly associated with constitutive heterochromatin structures. This association appears physiologically relevant since the association of YY1 with pericentromeric gamma-satellite DNA observed in cycling 3T3 fibroblasts strongly diminished in quiescent (G0) 3T3 fibroblasts. We discuss the implications of these results in the context of heterochromatin formation as well as with regard to the YY1-induced repression of euchromatic genes.

  • Transcription Factor YY1 associates with pericentromeric gamma-satellite DNA in cycling but not in quiescent (G0) cells.
    Nucleic Acids Research, 2004
    Co-Authors: Elena A Shestakova, Zeyni Mansuroglu, Houda Mokrani, Nicolae Ghinea, Eliette Bonnefoy
    Abstract:

    Pericentromeric gamma-satellite DNA is organized in constitutive heterochromatin structures. It comprises a 234 bp sequence repeated several thousands times surrounding the centromeric sequence of all murine chromosomes. Potential binding sites for Transcription Factor Yin Yang 1 (YY1), a repressor or activator of several cellular and viral genes, are present in pericentromeric gamma-satellite DNA. Using gel retardation and chromatin immunoprecipitation, we demonstrate in this work that YY1 specifically interacts in vitro and in vivo with gamma-satellite DNA. Using immunoFISH and confocal microscopy we show that YY1 specifically co-localizes with pericentromeric gamma-satellite DNA clusters organized in constitutive heterochromatin in murine L929 and 3T3 fibroblasts cell lines. Immunoelectron microscopy experiments further confirmed YY1 localization in heterochromatic areas. Overall, our results demonstrate for the first time that a fraction of YY1 is directly associated with constitutive heterochromatin structures. This association appears physiologically relevant since the association of YY1 with pericentromeric gamma-satellite DNA observed in cycling 3T3 fibroblasts strongly diminished in quiescent (G0) 3T3 fibroblasts. We discuss the implications of these results in the context of heterochromatin formation as well as with regard to the YY1-induced repression of euchromatic genes.

Yujiang Shi - One of the best experts on this subject based on the ideXlab platform.

  • a YY1 ino80 complex regulates genomic stability through homologous recombination based repair
    Nature Structural & Molecular Biology, 2007
    Co-Authors: Peter Mulligan, Yang Shi, Yujiang Shi, Joseph Landry, Weijia Wang, Jac A Nickoloff, Huifei Liu
    Abstract:

    DNA damage repair is crucial for the maintenance of genome integrity and cancer suppression. We found that loss of the mouse Transcription Factor YY1 resulted in polyploidy and chromatid aberrations, which are signatures of defects in homologous recombination. Further biochemical analyses identified a YY1 complex comprising components of the evolutionarily conserved INO80 chromatin-remodeling complex. Notably, RNA interference–mediated knockdown of YY1 and INO80 increased cellular sensitivity toward DNA-damaging agents. Functional assays revealed that both YY1 and INO80 are essential in homologous recombination–based DNA repair (HRR), which was further supported by the finding that YY1 preferentially bound a recombination-intermediate structure in vitro. Collectively, these observations reveal a link between YY1 and INO80 and roles for both in HRR, providing new insight into mechanisms that control the cellular response to genotoxic stress.

  • A YY1–INO80 complex regulates genomic stability through homologous recombination–based repair
    Nature structural & molecular biology, 2007
    Co-Authors: Huifei Liu, Yujiang Shi, Peter Mulligan, Joseph Landry, Weijia Wang, Jac A Nickoloff
    Abstract:

    DNA damage repair is crucial for the maintenance of genome integrity and cancer suppression. We found that loss of the mouse Transcription Factor YY1 resulted in polyploidy and chromatid aberrations, which are signatures of defects in homologous recombination. Further biochemical analyses identified a YY1 complex comprising components of the evolutionarily conserved INO80 chromatin-remodeling complex. Notably, RNA interference–mediated knockdown of YY1 and INO80 increased cellular sensitivity toward DNA-damaging agents. Functional assays revealed that both YY1 and INO80 are essential in homologous recombination–based DNA repair (HRR), which was further supported by the finding that YY1 preferentially bound a recombination-intermediate structure in vitro. Collectively, these observations reveal a link between YY1 and INO80 and roles for both in HRR, providing new insight into mechanisms that control the cellular response to genotoxic stress.

Mofang Liu - One of the best experts on this subject based on the ideXlab platform.

  • kras nf κb YY1 mir 489 signaling axis controls pancreatic cancer metastasis
    Cancer Research, 2017
    Co-Authors: Peng Yuan, Ye Fei Rong, Jing Cao, Yingbin Liu, Wenhui Lou, Mofang Liu
    Abstract:

    KRAS activation occurring in more than 90% of pancreatic ductal adenocarcinomas (PDAC) drives progression and metastasis, but the underlying mechanisms involved in these processes are still poorly understood. Here, we show how KRAS acts through inflammatory NF-κB signaling to activate the Transcription Factor YY1, which represses expression of the tumor suppressor gene miR-489. In PDAC cells, repression of miR-489 by KRAS signaling inhibited migration and metastasis by targeting the extracellular matrix Factors ADAM9 and MMP7. miR-489 downregulation elevated levels of ADAM9 and MMP7, thereby enhancing the migration and metastasis of PDAC cells. Together, our results establish a pivotal mechanism of PDAC metastasis and suggest miR-489 as a candidate therapeutic target for their attack. Cancer Res; 77(1); 100-11. ©2016 AACR.

  • KRAS/NF-κB/YY1/miR-489 signaling axis controls pancreatic cancer metastasis
    Cancer research, 2016
    Co-Authors: Peng Yuan, Ye Fei Rong, Jing Cao, Yingbin Liu, Wenhui Lou, Mofang Liu
    Abstract:

    KRAS activation occurring in more than 90% of pancreatic ductal adenocarcinomas (PDAC) drives progression and metastasis, but the underlying mechanisms involved in these processes are still poorly understood. Here, we show how KRAS acts through inflammatory NF-κB signaling to activate the Transcription Factor YY1, which represses expression of the tumor suppressor gene miR-489. In PDAC cells, repression of miR-489 by KRAS signaling inhibited migration and metastasis by targeting the extracellular matrix Factors ADAM9 and MMP7. miR-489 downregulation elevated levels of ADAM9 and MMP7, thereby enhancing the migration and metastasis of PDAC cells. Together, our results establish a pivotal mechanism of PDAC metastasis and suggest miR-489 as a candidate therapeutic target for their attack. Cancer Res; 77(1); 100-11. ©2016 AACR.