The Experts below are selected from a list of 41754 Experts worldwide ranked by ideXlab platform
Kathryn Calame - One of the best experts on this subject based on the ideXlab platform.
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Transcriptional Repressor blimp 1 regulates t cell homeostasis and function
Nature Immunology, 2006Co-Authors: Gislâine A. Martins, Luisa Cimmino, Matthias Szabolcs, Alan Herron, Erna Magnusdottir, Miriam Shapiroshelef, Kathryn CalameAbstract:The B lymphocyte–induced maturation protein 1 (Blimp-1) Transcriptional Repressor is required for terminal differentiation of B lymphocytes. Here we document a function for Blimp-1 in the T cell lineage. Blimp-1-deficient thymocytes showed decreased survival and Blimp-1-deficient mice had more peripheral effector T cells. Mice lacking Blimp-1 developed severe colitis as early as 6 weeks of age, and Blimp-1-deficient regulatory T cells were defective in blocking the development of colitis. Blimp-1 mRNA expression increased substantially in response to T cell receptor stimulation. Compared with wild-type CD4+ T cells, Blimp-1-deficient CD4+ T cells proliferated more and produced excess interleukin 2 and interferon-γ but reduced interleukin 10 after T cell receptor stimulation. These results emphasize a crucial function for Blimp-1 in controlling T cell homeostasis and activation.
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Transcriptional Repressor Blimp-1 regulates T cell homeostasis and function
Nature Immunology, 2006Co-Authors: Gislâine A. Martins, Luisa Cimmino, Miriam Shapiro-shelef, Matthias Szabolcs, Alan Herron, Erna Magnusdottir, Kathryn CalameAbstract:The B lymphocyte-induced maturation protein 1 (Blimp-1) Transcriptional Repressor is required for terminal differentiation of B lymphocytes. Here we document a function for Blimp-1 in the T cell lineage. Blimp-1-deficient thymocytes showed decreased survival and Blimp-1-deficient mice had more peripheral effector T cells. Mice lacking Blimp-1 developed severe colitis as early as 6 weeks of age, and Blimp-1-deficient regulatory T cells were defective in blocking the development of colitis. Blimp-1 mRNA expression increased substantially in response to T cell receptor stimulation. Compared with wild-type CD4+T cells, Blimp-1-deficient CD4+T cells proliferated more and produced excess interleukin 2 and interferon-γ but reduced interleukin 10 after T cell receptor stimulation. These results emphasize a crucial function for Blimp-1 in controlling T cell homeostasis and activation. © 2006 Nature Publishing Group.
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Transcriptional Repressor zf5 identifies a new conserved domain in zinc finger proteins
Nucleic Acids Research, 1993Co-Authors: Michitaka Numoto, Ohtsura Niwa, Jonthan Kaplan, Kwokkin Wrong, Kevin Merrell, Kenji Kamiya, Kazuyoshi Yanagihara, Kathryn CalameAbstract:Abstract We have cloned a cDNA encoding a new murine C2H2 zinc finger protein, ZF5. The 51.3 kD protein contains five GL1-Kruppel type zinc fingers at the C-terminus. At its N-terminus, ZF5 has a 41 amino acid region which was found to be homologous to the N-termini of several other zinc finger proteins. This region defines a new motif within zinc finger proteins which we have named the Zinc finger N-terminal (ZiN) domain. ZF5 binds to two sites in the c-myc promoter and to the -50 bp site of the herpes simplex thymidine kinase promoter. ZF5 is a Transcriptional Repressor and its repression domain is located N-terminal to the zinc finger domains. A single 4 kb ZF5 mRNA is expressed widely.
Ichio Shimada - One of the best experts on this subject based on the ideXlab platform.
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conformational equilibrium defines the variable induction of the multidrug binding Transcriptional Repressor qacr
Proceedings of the National Academy of Sciences of the United States of America, 2019Co-Authors: Koh Takeuchi, Misaki Imai, Ichio ShimadaAbstract:QacR, a multidrug-binding Transcriptional Repressor in pathogenic bacteria Staphylococcus aureus, modulates the Transcriptional level of the multidrug transporter gene, qacA, in response to engaging a set of diverse ligands. However, the structural basis that defines the variable induction level remains unknown. Here, we reveal that the conformational equilibrium between the repressive and inducive conformations in QacR defines the induction level of the transporter gene. In addition, the unligated QacR is already partly populated in the inducive conformation, allowing the basal expression of the transporter. We also showed that, in the known constitutively active QacR mutants, the equilibrium is shifted more toward the inducive conformation, even in the unligated state. These results highlight the unexpected structural mechanism, connecting the promiscuous multidrug binding to the variable Transcriptional regulation of QacR, which provide clues to dysfunctioning of the multidrug resistance systems.
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Dynamic equilibrium on DNA defines Transcriptional regulation of a multidrug binding Transcriptional Repressor, LmrR
Scientific Reports, 2017Co-Authors: Koh Takeuchi, Misaki Imai, Ichio ShimadaAbstract:LmrR is a multidrug binding Transcriptional Repressor that controls the expression of a major multidrug transporter, LmrCD, in Lactococcus lactis. Promiscuous compound ligations reduce the affinity of LmrR for the lmrCD operator by several fold to release the Transcriptional repression; however, the affinity reduction is orders of magnitude smaller than that of typical Transcriptional Repressors. Here, we found that the Transcriptional regulation of LmrR is achieved through an equilibrium between the operator-bound and non-specific DNA-adsorption states in vivo. The effective dissociation constant of LmrR for the lmrCD operator under the equilibrium is close to the endogenous concentration of LmrR, which allows a substantial reduction of LmrR occupancy upon compound ligations. Therefore, LmrR represents a dynamic type of Transcriptional regulation of prokaryotic multidrug resistance systems, where the small affinity reduction induced by compounds is coupled to the functional relocalization of the Repressor on the genomic DNA via nonspecific DNA adsorption.
Shuichi Yanagisawa - One of the best experts on this subject based on the ideXlab platform.
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characterization of a nitrate inducible Transcriptional Repressor nigt1 provides new insights into dna recognition by the garp family proteins
Plant Signaling & Behavior, 2013Co-Authors: Shuichi YanagisawaAbstract:The GARP domain is a single Myb-related DNA-binding domain found in plant transcription factors. Proteins containing the GARP domain (GARP family proteins) are suggested to be involved in the regulation of various physiological processes through their interactions with ostensibly different DNA sequences. Our recent study on a nitrate-inducible gene encoding a GARP family protein, referred to as NIGT1 (Nitrate-Inducible, GARP-type Transcriptional Repressor 1), not only suggests a previously unidentified role for the GARP family proteins in higher plants but also provides a hypothesis for why NIGT1 can show dual specificity on DNA binding and why respective GARP family proteins can recognize very different DNA sequences.
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A Nitrate-Inducible GARP Family Gene Encodes an Auto-Repressible Transcriptional Repressor in Rice
Plant and Cell Physiology, 2013Co-Authors: Naoya Sawaki, Ryoma Tsujimoto, Mikao Shigyo, Mineko Konishi, Seiichi Toki, Toru Fujiwara, Shuichi YanagisawaAbstract:Nitrogen is the most important macronutrient in plants and its supply induces responses in gene expression, metabolism and developmental processes. However, the molecular mechanisms underlying the nitrogen responses remain poorly understood. Here we show that the supply of nitrate but not ammonium immediately induces the expression of a Transcriptional Repressor gene in rice, designated NIGT1 (Nitrate-Inducible, GARP-type Transcriptional Repressor 1). The results of DNA-binding site selection experiments and electrophoretic mobility shift assays indicated that NIGT1 binds to DNA containing either of two consensus sequences, GAATC or GAATATTC. In transient reporter assays, NIGT1 was found to repress transcription from the promoters containing the identified NIGT1-binding sequences in vivo. Furthermore, NIGT1 repressed the activity of its own promoter, suggesting an autorepression mechanism. Consistently, nitrate-induced NIGT1 expression was found to be down-regulated after a transient peak during nitrate treatment, and the nitrate-induced expression of NIGT1 decreased in transgenic rice plants in which this gene was constitutively overexpressed. Furthermore, the chlorophyll content that could be a marker of nitrogen utilization was found to be decreased in NIGT1 overexpressors of rice grown with nitrate medium but not with ammonium medium. Thus, we propose NIGT1 as a nitrate-inducible and autorepressible Transcriptional Repressor that may play a role in the nitrogen response in rice. Taken together with the fact that the NIGT1-binding sites are conserved in promoter sequences of Arabidopsis NIGT1 homologs, our findings imply the presence of a time-dependent complex system for nitrate-responsive Transcriptional regulation that is conserved in both monocots and dicots.
Stephen L. Nutt - One of the best experts on this subject based on the ideXlab platform.
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Transcriptional Repressor blimp 1 is essential for t cell homeostasis and self tolerance
Nature Immunology, 2006Co-Authors: Axel Kallies, Edwin D. Hawkins, Philip D. Hodgkin, Mirja Hommel, Donald Metcalf, Gabrielle T Belz, Lynn M Corcoran, Stephen L. NuttAbstract:T cell homeostasis is crucial for a functional immune system, as the accumulation of T cells resulting from lack of regulatory T cells or an inability to shut down immune responses can lead to inflammation and autoimmune pathology. Here we show that Blimp-1, a Transcriptional Repressor that is a 'master regulator' of terminal B cell differentiation, was expressed in a subset of antigen-experienced CD4+ and CD8+ T cells. Mice reconstituted with fetal liver stem cells expressing a mutant Blimp-1 lacking the DNA-binding domain developed a lethal multiorgan inflammatory disease caused by an accumulation of effector and memory T cells. These data identify Blimp-1 as an essential regulator of T cell homeostasis and suggest that Blimp-1 regulates both B cell and T cell differentiation.
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Transcriptional Repressor Blimp-1 is essential for T cell homeostasis and self-tolerance
Nature Immunology, 2006Co-Authors: Axel Kallies, Edwin D. Hawkins, Philip D. Hodgkin, Mirja Hommel, Donald Metcalf, Gabrielle T Belz, Lynn M Corcoran, Stephen L. NuttAbstract:T cell homeostasis is crucial for a functional immune system, as the accumulation of T cells resulting from lack of regulatory T cells or an inability to shut down immune responses can lead to inflammation and autoimmune pathology. Here we show that Blimp-1, a Transcriptional Repressor that is a 'master regulator' of terminal B cell differentiation, was expressed in a subset of antigen-experienced CD4+and CD8+T cells. Mice reconstituted with fetal liver stem cells expressing a mutant Blimp-1 lacking the DNA-binding domain developed a lethal multiorgan inflammatory disease caused by an accumulation of effector and memory T cells. These data identify Blimp-1 as an essential regulator of T cell homeostasis and suggest that Blimp-1 regulates both B cell and T cell differentiation. © 2006 Nature Publishing Group.
Koh Takeuchi - One of the best experts on this subject based on the ideXlab platform.
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conformational equilibrium defines the variable induction of the multidrug binding Transcriptional Repressor qacr
Proceedings of the National Academy of Sciences of the United States of America, 2019Co-Authors: Koh Takeuchi, Misaki Imai, Ichio ShimadaAbstract:QacR, a multidrug-binding Transcriptional Repressor in pathogenic bacteria Staphylococcus aureus, modulates the Transcriptional level of the multidrug transporter gene, qacA, in response to engaging a set of diverse ligands. However, the structural basis that defines the variable induction level remains unknown. Here, we reveal that the conformational equilibrium between the repressive and inducive conformations in QacR defines the induction level of the transporter gene. In addition, the unligated QacR is already partly populated in the inducive conformation, allowing the basal expression of the transporter. We also showed that, in the known constitutively active QacR mutants, the equilibrium is shifted more toward the inducive conformation, even in the unligated state. These results highlight the unexpected structural mechanism, connecting the promiscuous multidrug binding to the variable Transcriptional regulation of QacR, which provide clues to dysfunctioning of the multidrug resistance systems.
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Dynamic equilibrium on DNA defines Transcriptional regulation of a multidrug binding Transcriptional Repressor, LmrR
Scientific Reports, 2017Co-Authors: Koh Takeuchi, Misaki Imai, Ichio ShimadaAbstract:LmrR is a multidrug binding Transcriptional Repressor that controls the expression of a major multidrug transporter, LmrCD, in Lactococcus lactis. Promiscuous compound ligations reduce the affinity of LmrR for the lmrCD operator by several fold to release the Transcriptional repression; however, the affinity reduction is orders of magnitude smaller than that of typical Transcriptional Repressors. Here, we found that the Transcriptional regulation of LmrR is achieved through an equilibrium between the operator-bound and non-specific DNA-adsorption states in vivo. The effective dissociation constant of LmrR for the lmrCD operator under the equilibrium is close to the endogenous concentration of LmrR, which allows a substantial reduction of LmrR occupancy upon compound ligations. Therefore, LmrR represents a dynamic type of Transcriptional regulation of prokaryotic multidrug resistance systems, where the small affinity reduction induced by compounds is coupled to the functional relocalization of the Repressor on the genomic DNA via nonspecific DNA adsorption.
