The Experts below are selected from a list of 3201 Experts worldwide ranked by ideXlab platform
Madhurendra Singh - One of the best experts on this subject based on the ideXlab platform.
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gα i3 signaling is associated with sexual dimorphic expression of the clock controlled output Gene DBP in murine liver
Oncotarget, 2018Co-Authors: Madhurendra Singh, Laura Bergmann, Alexander Lang, Katja Pexa, Fabian Kuck, Dennis Stibane, Linda Janke, Hakima Ezzahoini, Antje LindeckeAbstract:The albumin D-box binding protein (DBP) is a member of the PAR bZip (proline and acidic amino acid-rich basic leucine zipper) transcription factor family and functions as important regulator of circadian core and output Gene expression. Gene expression of DBP itself is under the control of E-box-dependent binding by the Bmal1-Clock heterodimer and CRE-dependent binding by the cAMP responsive element binding protein (CREB). However, the signaling mechanism mediating CREB-dependent regulation of DBP expression in the peripheral clock remains elusive. In this study, we examined the role of the GPCR (G-protein-coupled receptor)/Gαi3 (Galphai3) controlled cAMP-CREB signaling pathway in the regulation of hepatic expression of core clock and clock-regulated Genes, including DBP. Analysis of circadian Gene expression revealed that rhythmicity of hepatic transcript levels of the majority of core clock (including Per1) and clock-regulated Genes were not affected by Gαi3 deficiency. Consistently, the period length of primary Gαi3 deficient tail fibroblasts expressing a Bmal1-Luciferase reporter was not affected. Interestingly, however, Gαi3 deficient female but not male mice showed a tendentiously increased activation of CREB (nuclear pSer133-CREB) accompanied by an advanced peak in DBP Gene expression and elevated mRNA levels of the cytochrome P450 family member Cyp3a11, a target Gene of DBP. Accordingly, selective inhibition of CREB led to a strongly decreased expression of DBP and CYP3A4 (human Cyp3a11 homologue) in HepG2 liver cells. In summary, our data suggest that the Gαi3-pCREB signalling pathway functions as a regulator of sexual-dimorphic expression of DBP and its xenobiotic target enzymes Cyp3a11/CYP3A4.
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gαi3 signaling is associated with sexual dimorphic expression of the clock controlled output Gene DBP in murine liver
Oncotarget, 2018Co-Authors: Madhurendra Singh, Laura Bergmann, Alexander Lang, Katja Pexa, Fabian Kuck, Dennis Stibane, Linda Janke, Hakima Ezzahoini, Antje LindeckeAbstract:// Madhurendra Singh 1, 8 , Laura Bergmann 1 , Alexander Lang 1 , Katja Pexa 1 , Fabian Kuck 1 , Dennis Stibane 1 , Linda Janke 5 , Hakima Ezzahoini 1 , Antje Lindecke 2 , Constanze Wiek 3 , Helmut Hanenberg 3, 7 , Karl Kohrer 2 , Charlotte von Gall 4 , Hans Reinke 5, 6 and Roland P. Piekorz 1 1 Institut fur Biochemie und Molekularbiologie II, Medizinische Fakultat der Heinrich-Heine-Universitat, Dusseldorf, Germany 2 Biologisch-Medizinisches Forschungszentrum (BMFZ), Medizinische Fakultat der Heinrich-Heine-Universitat, Dusseldorf, Germany 3 Hals-Nasen-Ohren-Klinik, Medizinische Fakultat der Heinrich-Heine-Universitat, Dusseldorf, Germany 4 Institut fur Anatomie II, Medizinische Fakultat der Heinrich-Heine-Universitat, Dusseldorf, Germany 5 Institut fur Klinische Chemie und Laboratoriumsmedizin, Medizinische Fakultat der Heinrich-Heine-Universitat, Dusseldorf, Germany 6 IUF – Leibniz Institut fur Umweltmedizinische Forschung, Dusseldorf, Germany 7 Klinik fur Kinderheilkunde III, Universitatsklinikum Essen, Universitat Duisburg-Essen, Essen, Germany 8 Current address: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden Correspondence to: Roland P. Piekorz, email: Roland.Piekorz@hhu.de Keywords: circadian regulation; galphai3/GNAI3; CREB; cytochrome P450; albumin D-box binding protein; Pathology Received: February 07, 2017 Accepted: June 14, 2018 Published: July 13, 2018 ABSTRACT The albumin D-box binding protein (DBP) is a member of the PAR bZip (proline and acidic amino acid-rich basic leucine zipper) transcription factor family and functions as important regulator of circadian core and output Gene expression. Gene expression of DBP itself is under the control of E-box-dependent binding by the Bmal1-Clock heterodimer and CRE-dependent binding by the cAMP responsive element binding protein (CREB). However, the signaling mechanism mediating CREB-dependent regulation of DBP expression in the peripheral clock remains elusive. In this study, we examined the role of the GPCR (G-protein-coupled receptor)/Gα i3 (Galphai3) controlled cAMP-CREB signaling pathway in the regulation of hepatic expression of core clock and clock-regulated Genes, including DBP . Analysis of circadian Gene expression revealed that rhythmicity of hepatic transcript levels of the majority of core clock (including Per1) and clock-regulated Genes were not affected by Gα i3 deficiency. Consistently, the period length of primary Gα i3 deficient tail fibroblasts expressing a Bmal1-Luciferase reporter was not affected. Interestingly, however, Gα i3 deficient female but not male mice showed a tendentiously increased activation of CREB (nuclear pSer133-CREB) accompanied by an advanced peak in DBP Gene expression and elevated mRNA levels of the cytochrome P 450 family member Cyp3a11, a target Gene of DBP. Accordingly, selective inhibition of CREB led to a strongly decreased expression of DBP and CYP3A4 (human Cyp3a11 homologue) in HepG2 liver cells. In summary, our data suggest that the Gα i3 -pCREB signalling pathway functions as a regulator of sexual-dimorphic expression of DBP and its xenobiotic target enzymes Cyp3a11/CYP3A4.
Paolo Sassonecorsi - One of the best experts on this subject based on the ideXlab platform.
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cycles in spatial and temporal chromosomal organization driven by the circadian clock
Nature Structural & Molecular Biology, 2013Co-Authors: Lorena Aguilararnal, Ofir Hakim, Vishal R Patel, Pierre Baldi, Gordon L Hager, Paolo SassonecorsiAbstract:4C (chromosome conformation capture on chip) analyses using the clock-controlled DBP Gene as bait reveal the existence of circadian long-range interactions in mouse embryonic fibroblasts. The DBP circadian interactome is dependent on a functional circadian clock and contains a number of clock-related DNA elements.
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cycles in spatial and temporal chromosomal organization driven by the circadian clock
Nature Structural & Molecular Biology, 2013Co-Authors: Lorena Aguilararnal, Ofir Hakim, Vishal R Patel, Pierre Baldi, Gordon L Hager, Paolo SassonecorsiAbstract:Dynamic transitions in the epigenome have been associated with regulated patterns of nuclear organization. The accumulating evidence that chromatin remodeling is implicated in circadian function prompted us to explore whether the clock may control nuclear architecture. We applied the chromosome conformation capture on chip technology in mouse embryonic fibroblasts (MEFs) to demonstrate the presence of circadian long-range interactions using the clock-controlled DBP Gene as bait. The circadian genomic interactions with DBP were highly specific and were absent in MEFs whose clock was disrupted by ablation of the Bmal1 Gene (also called Arntl). We establish that the DBP circadian interactome contains a wide variety of Genes and clock-related DNA elements. These findings reveal a previously unappreciated circadian and clock-dependent shaping of the nuclear landscape.
Ofir Hakim - One of the best experts on this subject based on the ideXlab platform.
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cycles in spatial and temporal chromosomal organization driven by the circadian clock
Nature Structural & Molecular Biology, 2013Co-Authors: Lorena Aguilararnal, Ofir Hakim, Vishal R Patel, Pierre Baldi, Gordon L Hager, Paolo SassonecorsiAbstract:4C (chromosome conformation capture on chip) analyses using the clock-controlled DBP Gene as bait reveal the existence of circadian long-range interactions in mouse embryonic fibroblasts. The DBP circadian interactome is dependent on a functional circadian clock and contains a number of clock-related DNA elements.
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cycles in spatial and temporal chromosomal organization driven by the circadian clock
Nature Structural & Molecular Biology, 2013Co-Authors: Lorena Aguilararnal, Ofir Hakim, Vishal R Patel, Pierre Baldi, Gordon L Hager, Paolo SassonecorsiAbstract:Dynamic transitions in the epigenome have been associated with regulated patterns of nuclear organization. The accumulating evidence that chromatin remodeling is implicated in circadian function prompted us to explore whether the clock may control nuclear architecture. We applied the chromosome conformation capture on chip technology in mouse embryonic fibroblasts (MEFs) to demonstrate the presence of circadian long-range interactions using the clock-controlled DBP Gene as bait. The circadian genomic interactions with DBP were highly specific and were absent in MEFs whose clock was disrupted by ablation of the Bmal1 Gene (also called Arntl). We establish that the DBP circadian interactome contains a wide variety of Genes and clock-related DNA elements. These findings reveal a previously unappreciated circadian and clock-dependent shaping of the nuclear landscape.
Antje Lindecke - One of the best experts on this subject based on the ideXlab platform.
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gα i3 signaling is associated with sexual dimorphic expression of the clock controlled output Gene DBP in murine liver
Oncotarget, 2018Co-Authors: Madhurendra Singh, Laura Bergmann, Alexander Lang, Katja Pexa, Fabian Kuck, Dennis Stibane, Linda Janke, Hakima Ezzahoini, Antje LindeckeAbstract:The albumin D-box binding protein (DBP) is a member of the PAR bZip (proline and acidic amino acid-rich basic leucine zipper) transcription factor family and functions as important regulator of circadian core and output Gene expression. Gene expression of DBP itself is under the control of E-box-dependent binding by the Bmal1-Clock heterodimer and CRE-dependent binding by the cAMP responsive element binding protein (CREB). However, the signaling mechanism mediating CREB-dependent regulation of DBP expression in the peripheral clock remains elusive. In this study, we examined the role of the GPCR (G-protein-coupled receptor)/Gαi3 (Galphai3) controlled cAMP-CREB signaling pathway in the regulation of hepatic expression of core clock and clock-regulated Genes, including DBP. Analysis of circadian Gene expression revealed that rhythmicity of hepatic transcript levels of the majority of core clock (including Per1) and clock-regulated Genes were not affected by Gαi3 deficiency. Consistently, the period length of primary Gαi3 deficient tail fibroblasts expressing a Bmal1-Luciferase reporter was not affected. Interestingly, however, Gαi3 deficient female but not male mice showed a tendentiously increased activation of CREB (nuclear pSer133-CREB) accompanied by an advanced peak in DBP Gene expression and elevated mRNA levels of the cytochrome P450 family member Cyp3a11, a target Gene of DBP. Accordingly, selective inhibition of CREB led to a strongly decreased expression of DBP and CYP3A4 (human Cyp3a11 homologue) in HepG2 liver cells. In summary, our data suggest that the Gαi3-pCREB signalling pathway functions as a regulator of sexual-dimorphic expression of DBP and its xenobiotic target enzymes Cyp3a11/CYP3A4.
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gαi3 signaling is associated with sexual dimorphic expression of the clock controlled output Gene DBP in murine liver
Oncotarget, 2018Co-Authors: Madhurendra Singh, Laura Bergmann, Alexander Lang, Katja Pexa, Fabian Kuck, Dennis Stibane, Linda Janke, Hakima Ezzahoini, Antje LindeckeAbstract:// Madhurendra Singh 1, 8 , Laura Bergmann 1 , Alexander Lang 1 , Katja Pexa 1 , Fabian Kuck 1 , Dennis Stibane 1 , Linda Janke 5 , Hakima Ezzahoini 1 , Antje Lindecke 2 , Constanze Wiek 3 , Helmut Hanenberg 3, 7 , Karl Kohrer 2 , Charlotte von Gall 4 , Hans Reinke 5, 6 and Roland P. Piekorz 1 1 Institut fur Biochemie und Molekularbiologie II, Medizinische Fakultat der Heinrich-Heine-Universitat, Dusseldorf, Germany 2 Biologisch-Medizinisches Forschungszentrum (BMFZ), Medizinische Fakultat der Heinrich-Heine-Universitat, Dusseldorf, Germany 3 Hals-Nasen-Ohren-Klinik, Medizinische Fakultat der Heinrich-Heine-Universitat, Dusseldorf, Germany 4 Institut fur Anatomie II, Medizinische Fakultat der Heinrich-Heine-Universitat, Dusseldorf, Germany 5 Institut fur Klinische Chemie und Laboratoriumsmedizin, Medizinische Fakultat der Heinrich-Heine-Universitat, Dusseldorf, Germany 6 IUF – Leibniz Institut fur Umweltmedizinische Forschung, Dusseldorf, Germany 7 Klinik fur Kinderheilkunde III, Universitatsklinikum Essen, Universitat Duisburg-Essen, Essen, Germany 8 Current address: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden Correspondence to: Roland P. Piekorz, email: Roland.Piekorz@hhu.de Keywords: circadian regulation; galphai3/GNAI3; CREB; cytochrome P450; albumin D-box binding protein; Pathology Received: February 07, 2017 Accepted: June 14, 2018 Published: July 13, 2018 ABSTRACT The albumin D-box binding protein (DBP) is a member of the PAR bZip (proline and acidic amino acid-rich basic leucine zipper) transcription factor family and functions as important regulator of circadian core and output Gene expression. Gene expression of DBP itself is under the control of E-box-dependent binding by the Bmal1-Clock heterodimer and CRE-dependent binding by the cAMP responsive element binding protein (CREB). However, the signaling mechanism mediating CREB-dependent regulation of DBP expression in the peripheral clock remains elusive. In this study, we examined the role of the GPCR (G-protein-coupled receptor)/Gα i3 (Galphai3) controlled cAMP-CREB signaling pathway in the regulation of hepatic expression of core clock and clock-regulated Genes, including DBP . Analysis of circadian Gene expression revealed that rhythmicity of hepatic transcript levels of the majority of core clock (including Per1) and clock-regulated Genes were not affected by Gα i3 deficiency. Consistently, the period length of primary Gα i3 deficient tail fibroblasts expressing a Bmal1-Luciferase reporter was not affected. Interestingly, however, Gα i3 deficient female but not male mice showed a tendentiously increased activation of CREB (nuclear pSer133-CREB) accompanied by an advanced peak in DBP Gene expression and elevated mRNA levels of the cytochrome P 450 family member Cyp3a11, a target Gene of DBP. Accordingly, selective inhibition of CREB led to a strongly decreased expression of DBP and CYP3A4 (human Cyp3a11 homologue) in HepG2 liver cells. In summary, our data suggest that the Gα i3 -pCREB signalling pathway functions as a regulator of sexual-dimorphic expression of DBP and its xenobiotic target enzymes Cyp3a11/CYP3A4.
Lorena Aguilararnal - One of the best experts on this subject based on the ideXlab platform.
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cycles in spatial and temporal chromosomal organization driven by the circadian clock
Nature Structural & Molecular Biology, 2013Co-Authors: Lorena Aguilararnal, Ofir Hakim, Vishal R Patel, Pierre Baldi, Gordon L Hager, Paolo SassonecorsiAbstract:4C (chromosome conformation capture on chip) analyses using the clock-controlled DBP Gene as bait reveal the existence of circadian long-range interactions in mouse embryonic fibroblasts. The DBP circadian interactome is dependent on a functional circadian clock and contains a number of clock-related DNA elements.
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cycles in spatial and temporal chromosomal organization driven by the circadian clock
Nature Structural & Molecular Biology, 2013Co-Authors: Lorena Aguilararnal, Ofir Hakim, Vishal R Patel, Pierre Baldi, Gordon L Hager, Paolo SassonecorsiAbstract:Dynamic transitions in the epigenome have been associated with regulated patterns of nuclear organization. The accumulating evidence that chromatin remodeling is implicated in circadian function prompted us to explore whether the clock may control nuclear architecture. We applied the chromosome conformation capture on chip technology in mouse embryonic fibroblasts (MEFs) to demonstrate the presence of circadian long-range interactions using the clock-controlled DBP Gene as bait. The circadian genomic interactions with DBP were highly specific and were absent in MEFs whose clock was disrupted by ablation of the Bmal1 Gene (also called Arntl). We establish that the DBP circadian interactome contains a wide variety of Genes and clock-related DNA elements. These findings reveal a previously unappreciated circadian and clock-dependent shaping of the nuclear landscape.