The Experts below are selected from a list of 88317 Experts worldwide ranked by ideXlab platform

John Hiscott - One of the best experts on this subject based on the ideXlab platform.

  • selective DNA Binding and association with the creb Binding protein coactivator contribute to differential activation of alpha beta interferon genes by interferon regulatory factors 3 and 7
    Molecular and Cellular Biology, 2000
    Co-Authors: Pierre Genin, Yael Mamane, John Hiscott
    Abstract:

    Recent studies implicate the interferon (IFN) regulatory factors (IRF) IRF-3 and IRF-7 as key activators of the alpha/beta IFN (IFN-α/β) genes as well as the RANTES chemokine gene. Using coexpression analysis, the human IFNB, IFNA1, and RANTES promoters were stimulated by IRF-3 coexpression, whereas the IFNA4, IFNA7, and IFNA14 promoters were preferentially induced by IRF-7 only. Chimeric proteins containing combinations of different IRF-7 and IRF-3 domains were also tested, and the results provided evidence of distinct DNA Binding properties of IRF-3 and IRF-7, as well as a preferential association of IRF-3 with the CREB Binding protein (CBP) coactivator. Interestingly, some of these fusion proteins led to supraphysiological levels of IFN promoter activation. DNA Binding Site selection studies demonstrated that IRF-3 and IRF-7 bound to the 5′-GAAANNGAAANN-3′ consensus motif found in many virus-inducible genes; however, a single nucleotide substitution in either of the GAAA half-Site motifs eliminated IRF-3 Binding and transactivation activity but did not affect IRF-7 interaction or transactivation activity. These studies demonstrate that IRF-3 possesses a restricted DNA Binding Site specificity and interacts with CBP, whereas IRF-7 has a broader DNA Binding specificity that contributes to its capacity to stimulate delayed-type IFN gene expression. These results provide an explanation for the differential regulation of IFN-α/β gene expression by IRF-3 and IRF-7 and suggest that these factors have complementary rather than redundant roles in the activation of the IFN-α/β genes.

  • selective DNA Binding and association with the creb Binding protein coactivator contribute to differential activation of alpha beta interferon genes by interferon regulatory factors 3 and 7
    Molecular and Cellular Biology, 2000
    Co-Authors: Rongtuan Lin, Pierre Genin, Yael Mamane, John Hiscott
    Abstract:

    Recent studies implicate the interferon (IFN) regulatory factors (IRF) IRF-3 and IRF-7 as key activators of the alpha/beta IFN (IFN-alpha/beta) genes as well as the RANTES chemokine gene. Using coexpression analysis, the human IFNB, IFNA1, and RANTES promoters were stimulated by IRF-3 coexpression, whereas the IFNA4, IFNA7, and IFNA14 promoters were preferentially induced by IRF-7 only. Chimeric proteins containing combinations of different IRF-7 and IRF-3 domains were also tested, and the results provided evidence of distinct DNA Binding properties of IRF-3 and IRF-7, as well as a preferential association of IRF-3 with the CREB Binding protein (CBP) coactivator. Interestingly, some of these fusion proteins led to supraphysiological levels of IFN promoter activation. DNA Binding Site selection studies demonstrated that IRF-3 and IRF-7 bound to the 5'-GAAANNGAAANN-3' consensus motif found in many virus-inducible genes; however, a single nucleotide substitution in either of the GAAA half-Site motifs eliminated IRF-3 Binding and transactivation activity but did not affect IRF-7 interaction or transactivation activity. These studies demonstrate that IRF-3 possesses a restricted DNA Binding Site specificity and interacts with CBP, whereas IRF-7 has a broader DNA Binding specificity that contributes to its capacity to stimulate delayed-type IFN gene expression. These results provide an explanation for the differential regulation of IFN-alpha/beta gene expression by IRF-3 and IRF-7 and suggest that these factors have complementary rather than redundant roles in the activation of the IFN-alpha/beta genes.

Jikui Song - One of the best experts on this subject based on the ideXlab platform.

  • A Meier-Gorlin Syndrome Mutation Impairs the ORC1-Nucleosome Association
    ACS chemical biology, 2015
    Co-Authors: Wei Zhang, Or Gozani, Saumya M. Sankaran, Jikui Song
    Abstract:

    Recent studies have identified several genetic mutations within the BAH domain of human Origin Recognition Complex subunit 1 (hORC1BAH), including the R105Q mutation, implicated in Meier-Gorlin Syndrome (MGS). However, the pathological role of the hORC1 R105Q mutation remains unclear. In this study, we have investigated the interactions of the hORC1BAH domain with histone H4K20me2, DNA, and the nucleosome core particle labeled with H4Kc20me2, a chemical analog of H4K20me2. Our study revealed a nucleosomal DNA Binding Site for hORC1BAH. The R105Q mutation reduces the hORC1BAH-DNA Binding affinity, leading to impaired hORC1BAH-nucleosome interaction, which likely influences DNA replication initiation and MGS pathogenesis. This study provides an etiologic link between the hORC1 R105Q mutation and MGS.

  • A Meier-Gorlin Syndrome Mutation Impairs the ORC1-Nucleosome Association
    2015
    Co-Authors: Wei Zhang, Or Gozani, Saumya Sankaran, Jikui Song
    Abstract:

    Recent studies have identified several genetic mutations within the BAH domain of human Origin Recognition Complex subunit 1 (hORC1BAH), including the R105Q mutation, implicated in Meier-Gorlin Syndrome (MGS). However, the pathological role of the hORC1 R105Q mutation remains unclear. In this study, we have investigated the interactions of the hORC1BAH domain with histone H4K20me2, DNA, and the nucleosome core particle labeled with H4Kc20me2, a chemical analog of H4K20me2. Our study revealed a nucleosomal DNA Binding Site for hORC1BAH. The R105Q mutation reduces the hORC1BAH–DNA Binding affinity, leading to impaired hORC1BAH–nucleosome interaction, which likely influences DNA replication initiation and MGS pathogenesis. This study provides an etiologic link between the hORC1 R105Q mutation and MGS

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

  • selective DNA Binding and association with the creb Binding protein coactivator contribute to differential activation of alpha beta interferon genes by interferon regulatory factors 3 and 7
    Molecular and Cellular Biology, 2000
    Co-Authors: Pierre Genin, Yael Mamane, John Hiscott
    Abstract:

    Recent studies implicate the interferon (IFN) regulatory factors (IRF) IRF-3 and IRF-7 as key activators of the alpha/beta IFN (IFN-α/β) genes as well as the RANTES chemokine gene. Using coexpression analysis, the human IFNB, IFNA1, and RANTES promoters were stimulated by IRF-3 coexpression, whereas the IFNA4, IFNA7, and IFNA14 promoters were preferentially induced by IRF-7 only. Chimeric proteins containing combinations of different IRF-7 and IRF-3 domains were also tested, and the results provided evidence of distinct DNA Binding properties of IRF-3 and IRF-7, as well as a preferential association of IRF-3 with the CREB Binding protein (CBP) coactivator. Interestingly, some of these fusion proteins led to supraphysiological levels of IFN promoter activation. DNA Binding Site selection studies demonstrated that IRF-3 and IRF-7 bound to the 5′-GAAANNGAAANN-3′ consensus motif found in many virus-inducible genes; however, a single nucleotide substitution in either of the GAAA half-Site motifs eliminated IRF-3 Binding and transactivation activity but did not affect IRF-7 interaction or transactivation activity. These studies demonstrate that IRF-3 possesses a restricted DNA Binding Site specificity and interacts with CBP, whereas IRF-7 has a broader DNA Binding specificity that contributes to its capacity to stimulate delayed-type IFN gene expression. These results provide an explanation for the differential regulation of IFN-α/β gene expression by IRF-3 and IRF-7 and suggest that these factors have complementary rather than redundant roles in the activation of the IFN-α/β genes.

  • selective DNA Binding and association with the creb Binding protein coactivator contribute to differential activation of alpha beta interferon genes by interferon regulatory factors 3 and 7
    Molecular and Cellular Biology, 2000
    Co-Authors: Rongtuan Lin, Pierre Genin, Yael Mamane, John Hiscott
    Abstract:

    Recent studies implicate the interferon (IFN) regulatory factors (IRF) IRF-3 and IRF-7 as key activators of the alpha/beta IFN (IFN-alpha/beta) genes as well as the RANTES chemokine gene. Using coexpression analysis, the human IFNB, IFNA1, and RANTES promoters were stimulated by IRF-3 coexpression, whereas the IFNA4, IFNA7, and IFNA14 promoters were preferentially induced by IRF-7 only. Chimeric proteins containing combinations of different IRF-7 and IRF-3 domains were also tested, and the results provided evidence of distinct DNA Binding properties of IRF-3 and IRF-7, as well as a preferential association of IRF-3 with the CREB Binding protein (CBP) coactivator. Interestingly, some of these fusion proteins led to supraphysiological levels of IFN promoter activation. DNA Binding Site selection studies demonstrated that IRF-3 and IRF-7 bound to the 5'-GAAANNGAAANN-3' consensus motif found in many virus-inducible genes; however, a single nucleotide substitution in either of the GAAA half-Site motifs eliminated IRF-3 Binding and transactivation activity but did not affect IRF-7 interaction or transactivation activity. These studies demonstrate that IRF-3 possesses a restricted DNA Binding Site specificity and interacts with CBP, whereas IRF-7 has a broader DNA Binding specificity that contributes to its capacity to stimulate delayed-type IFN gene expression. These results provide an explanation for the differential regulation of IFN-alpha/beta gene expression by IRF-3 and IRF-7 and suggest that these factors have complementary rather than redundant roles in the activation of the IFN-alpha/beta genes.

Yael Mamane - One of the best experts on this subject based on the ideXlab platform.

  • selective DNA Binding and association with the creb Binding protein coactivator contribute to differential activation of alpha beta interferon genes by interferon regulatory factors 3 and 7
    Molecular and Cellular Biology, 2000
    Co-Authors: Pierre Genin, Yael Mamane, John Hiscott
    Abstract:

    Recent studies implicate the interferon (IFN) regulatory factors (IRF) IRF-3 and IRF-7 as key activators of the alpha/beta IFN (IFN-α/β) genes as well as the RANTES chemokine gene. Using coexpression analysis, the human IFNB, IFNA1, and RANTES promoters were stimulated by IRF-3 coexpression, whereas the IFNA4, IFNA7, and IFNA14 promoters were preferentially induced by IRF-7 only. Chimeric proteins containing combinations of different IRF-7 and IRF-3 domains were also tested, and the results provided evidence of distinct DNA Binding properties of IRF-3 and IRF-7, as well as a preferential association of IRF-3 with the CREB Binding protein (CBP) coactivator. Interestingly, some of these fusion proteins led to supraphysiological levels of IFN promoter activation. DNA Binding Site selection studies demonstrated that IRF-3 and IRF-7 bound to the 5′-GAAANNGAAANN-3′ consensus motif found in many virus-inducible genes; however, a single nucleotide substitution in either of the GAAA half-Site motifs eliminated IRF-3 Binding and transactivation activity but did not affect IRF-7 interaction or transactivation activity. These studies demonstrate that IRF-3 possesses a restricted DNA Binding Site specificity and interacts with CBP, whereas IRF-7 has a broader DNA Binding specificity that contributes to its capacity to stimulate delayed-type IFN gene expression. These results provide an explanation for the differential regulation of IFN-α/β gene expression by IRF-3 and IRF-7 and suggest that these factors have complementary rather than redundant roles in the activation of the IFN-α/β genes.

  • selective DNA Binding and association with the creb Binding protein coactivator contribute to differential activation of alpha beta interferon genes by interferon regulatory factors 3 and 7
    Molecular and Cellular Biology, 2000
    Co-Authors: Rongtuan Lin, Pierre Genin, Yael Mamane, John Hiscott
    Abstract:

    Recent studies implicate the interferon (IFN) regulatory factors (IRF) IRF-3 and IRF-7 as key activators of the alpha/beta IFN (IFN-alpha/beta) genes as well as the RANTES chemokine gene. Using coexpression analysis, the human IFNB, IFNA1, and RANTES promoters were stimulated by IRF-3 coexpression, whereas the IFNA4, IFNA7, and IFNA14 promoters were preferentially induced by IRF-7 only. Chimeric proteins containing combinations of different IRF-7 and IRF-3 domains were also tested, and the results provided evidence of distinct DNA Binding properties of IRF-3 and IRF-7, as well as a preferential association of IRF-3 with the CREB Binding protein (CBP) coactivator. Interestingly, some of these fusion proteins led to supraphysiological levels of IFN promoter activation. DNA Binding Site selection studies demonstrated that IRF-3 and IRF-7 bound to the 5'-GAAANNGAAANN-3' consensus motif found in many virus-inducible genes; however, a single nucleotide substitution in either of the GAAA half-Site motifs eliminated IRF-3 Binding and transactivation activity but did not affect IRF-7 interaction or transactivation activity. These studies demonstrate that IRF-3 possesses a restricted DNA Binding Site specificity and interacts with CBP, whereas IRF-7 has a broader DNA Binding specificity that contributes to its capacity to stimulate delayed-type IFN gene expression. These results provide an explanation for the differential regulation of IFN-alpha/beta gene expression by IRF-3 and IRF-7 and suggest that these factors have complementary rather than redundant roles in the activation of the IFN-alpha/beta genes.

Wei Zhang - One of the best experts on this subject based on the ideXlab platform.

  • A Meier-Gorlin Syndrome Mutation Impairs the ORC1-Nucleosome Association
    ACS chemical biology, 2015
    Co-Authors: Wei Zhang, Or Gozani, Saumya M. Sankaran, Jikui Song
    Abstract:

    Recent studies have identified several genetic mutations within the BAH domain of human Origin Recognition Complex subunit 1 (hORC1BAH), including the R105Q mutation, implicated in Meier-Gorlin Syndrome (MGS). However, the pathological role of the hORC1 R105Q mutation remains unclear. In this study, we have investigated the interactions of the hORC1BAH domain with histone H4K20me2, DNA, and the nucleosome core particle labeled with H4Kc20me2, a chemical analog of H4K20me2. Our study revealed a nucleosomal DNA Binding Site for hORC1BAH. The R105Q mutation reduces the hORC1BAH-DNA Binding affinity, leading to impaired hORC1BAH-nucleosome interaction, which likely influences DNA replication initiation and MGS pathogenesis. This study provides an etiologic link between the hORC1 R105Q mutation and MGS.

  • A Meier-Gorlin Syndrome Mutation Impairs the ORC1-Nucleosome Association
    2015
    Co-Authors: Wei Zhang, Or Gozani, Saumya Sankaran, Jikui Song
    Abstract:

    Recent studies have identified several genetic mutations within the BAH domain of human Origin Recognition Complex subunit 1 (hORC1BAH), including the R105Q mutation, implicated in Meier-Gorlin Syndrome (MGS). However, the pathological role of the hORC1 R105Q mutation remains unclear. In this study, we have investigated the interactions of the hORC1BAH domain with histone H4K20me2, DNA, and the nucleosome core particle labeled with H4Kc20me2, a chemical analog of H4K20me2. Our study revealed a nucleosomal DNA Binding Site for hORC1BAH. The R105Q mutation reduces the hORC1BAH–DNA Binding affinity, leading to impaired hORC1BAH–nucleosome interaction, which likely influences DNA replication initiation and MGS pathogenesis. This study provides an etiologic link between the hORC1 R105Q mutation and MGS