The Experts below are selected from a list of 10281 Experts worldwide ranked by ideXlab platform
John B. Gurdon - One of the best experts on this subject based on the ideXlab platform.
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histone variant macroh2a confers resistance to nuclear reprogramming
The EMBO Journal, 2011Co-Authors: Vincent Pasque, Astrid Gillich, Nigel Garrett, John B. GurdonAbstract:How various layers of Epigenetic Repression restrict somatic cell nuclear reprogramming is poorly understood. The transfer of mammalian somatic cell nuclei into Xenopus oocytes induces transcriptional reprogramming of previously repressed genes. Here, we address the mechanisms that restrict reprogramming following nuclear transfer by assessing the stability of the inactive X chromosome (Xi) in different stages of inactivation. We find that the Xi of mouse post‐implantation‐derived epiblast stem cells (EpiSCs) can be reversed by nuclear transfer, while the Xi of differentiated or extraembryonic cells is irreversible by nuclear transfer to oocytes. After nuclear transfer, Xist RNA is lost from chromatin of the Xi. Most Epigenetic marks such as DNA methylation and Polycomb‐deposited H3K27me3 do not explain the differences between reversible and irreversible Xi. Resistance to reprogramming is associated with incorporation of the histone variant macroH2A, which is retained on the Xi of differentiated cells, but absent from the Xi of EpiSCs. Our results uncover the decreased stability of the Xi in EpiSCs, and highlight the importance of combinatorial Epigenetic Repression involving macroH2A in restricting transcriptional reprogramming by oocytes. There is a [Have you seen?][1] (June 2011) associated with this Article. [1]: http://dx.doi.org/10.1038/emboj.2011.172
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Histone variant macroH2A confers resistance to nuclear reprogramming
The EMBO Journal, 2011Co-Authors: Vincent Pasque, Astrid Gillich, Nigel Garrett, John B. GurdonAbstract:How various layers of Epigenetic Repression restrict somatic cell nuclear reprogramming is poorly understood. The transfer of mammalian somatic cell nuclei into Xenopus oocytes induces transcriptional reprogramming of previously repressed genes. Here, we address the mechanisms that restrict reprogramming following nuclear transfer by assessing the stability of the inactive X chromosome (Xi) in different stages of inactivation. We find that the Xi of mouse post-implantation-derived epiblast stem cells (EpiSCs) can be reversed by nuclear transfer, while the Xi of differentiated or extraembryonic cells is irreversible by nuclear transfer to oocytes. After nuclear transfer, Xist RNA is lost from chromatin of the Xi. Most Epigenetic marks such as DNA methylation and Polycomb-deposited H3K27me3 do not explain the differences between reversible and irreversible Xi. Resistance to reprogramming is associated with incorporation of the histone variant macroH2A, which is retained on the Xi of differentiated cells, but absent from the Xi of EpiSCs. Our results uncover the decreased stability of the Xi in EpiSCs, and highlight the importance of combinatorial Epigenetic Repression involving macroH2A in restricting transcriptional reprogramming by oocytes.
Vincent Pasque - One of the best experts on this subject based on the ideXlab platform.
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histone variant macroh2a confers resistance to nuclear reprogramming
The EMBO Journal, 2011Co-Authors: Vincent Pasque, Astrid Gillich, Nigel Garrett, John B. GurdonAbstract:How various layers of Epigenetic Repression restrict somatic cell nuclear reprogramming is poorly understood. The transfer of mammalian somatic cell nuclei into Xenopus oocytes induces transcriptional reprogramming of previously repressed genes. Here, we address the mechanisms that restrict reprogramming following nuclear transfer by assessing the stability of the inactive X chromosome (Xi) in different stages of inactivation. We find that the Xi of mouse post‐implantation‐derived epiblast stem cells (EpiSCs) can be reversed by nuclear transfer, while the Xi of differentiated or extraembryonic cells is irreversible by nuclear transfer to oocytes. After nuclear transfer, Xist RNA is lost from chromatin of the Xi. Most Epigenetic marks such as DNA methylation and Polycomb‐deposited H3K27me3 do not explain the differences between reversible and irreversible Xi. Resistance to reprogramming is associated with incorporation of the histone variant macroH2A, which is retained on the Xi of differentiated cells, but absent from the Xi of EpiSCs. Our results uncover the decreased stability of the Xi in EpiSCs, and highlight the importance of combinatorial Epigenetic Repression involving macroH2A in restricting transcriptional reprogramming by oocytes. There is a [Have you seen?][1] (June 2011) associated with this Article. [1]: http://dx.doi.org/10.1038/emboj.2011.172
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Histone variant macroH2A confers resistance to nuclear reprogramming
The EMBO Journal, 2011Co-Authors: Vincent Pasque, Astrid Gillich, Nigel Garrett, John B. GurdonAbstract:How various layers of Epigenetic Repression restrict somatic cell nuclear reprogramming is poorly understood. The transfer of mammalian somatic cell nuclei into Xenopus oocytes induces transcriptional reprogramming of previously repressed genes. Here, we address the mechanisms that restrict reprogramming following nuclear transfer by assessing the stability of the inactive X chromosome (Xi) in different stages of inactivation. We find that the Xi of mouse post-implantation-derived epiblast stem cells (EpiSCs) can be reversed by nuclear transfer, while the Xi of differentiated or extraembryonic cells is irreversible by nuclear transfer to oocytes. After nuclear transfer, Xist RNA is lost from chromatin of the Xi. Most Epigenetic marks such as DNA methylation and Polycomb-deposited H3K27me3 do not explain the differences between reversible and irreversible Xi. Resistance to reprogramming is associated with incorporation of the histone variant macroH2A, which is retained on the Xi of differentiated cells, but absent from the Xi of EpiSCs. Our results uncover the decreased stability of the Xi in EpiSCs, and highlight the importance of combinatorial Epigenetic Repression involving macroH2A in restricting transcriptional reprogramming by oocytes.
Jongsook Kim Kemper - One of the best experts on this subject based on the ideXlab platform.
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a postprandial fgf19 shp lsd1 regulatory axis mediates Epigenetic Repression of hepatic autophagy
The EMBO Journal, 2017Co-Authors: Sangwon Byun, Jun Ichi Sadoshima, Byron Kemper, Bo Kong, Yang Zhang, Jongsook Kim KemperAbstract:Abstract Lysosome‐mediated autophagy is essential for cellular survival and homeostasis upon nutrient deprivation, but is repressed after feeding. Despite the emerging importance of transcriptional regulation of autophagy by nutrient‐sensing factors, the role for Epigenetic control is largely unexplored. Here, we show that Small Heterodimer Partner (SHP) mediates postprandial Epigenetic Repression of hepatic autophagy by recruiting histone demethylase LSD1 in response to a late fed‐state hormone, FGF19 (hFGF19, mFGF15). FGF19 treatment or feeding inhibits macroautophagy, including lipophagy, but these effects are blunted in SHP‐null mice or LSD1‐depleted mice. In addition, feeding‐mediated autophagy inhibition is attenuated in FGF15‐null mice. Upon FGF19 treatment or feeding, SHP recruits LSD1 to CREB‐bound autophagy genes, including Tfeb, resulting in dissociation of CRTC2, LSD1‐mediated demethylation of gene‐activation histone marks H3K4‐me2/3, and subsequent accumulation of repressive histone modifications. Both FXR and SHP inhibit hepatic autophagy interdependently, but while FXR acts early, SHP acts relatively late after feeding, which effectively sustains postprandial inhibition of autophagy. This study demonstrates that the FGF19‐SHP‐LSD1 axis maintains homeostasis by suppressing unnecessary autophagic breakdown of cellular components, including lipids, under nutrient‐rich postprandial conditions.
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A postprandial FGF19‐SHP‐LSD1 regulatory axis mediates Epigenetic Repression of hepatic autophagy
The EMBO Journal, 2017Co-Authors: Sangwon Byun, Jun Ichi Sadoshima, Byron Kemper, Bo Kong, Jian Ma, Yang Zhang, Jongsook Kim KemperAbstract:Abstract Lysosome‐mediated autophagy is essential for cellular survival and homeostasis upon nutrient deprivation, but is repressed after feeding. Despite the emerging importance of transcriptional regulation of autophagy by nutrient‐sensing factors, the role for Epigenetic control is largely unexplored. Here, we show that Small Heterodimer Partner (SHP) mediates postprandial Epigenetic Repression of hepatic autophagy by recruiting histone demethylase LSD1 in response to a late fed‐state hormone, FGF19 (hFGF19, mFGF15). FGF19 treatment or feeding inhibits macroautophagy, including lipophagy, but these effects are blunted in SHP‐null mice or LSD1‐depleted mice. In addition, feeding‐mediated autophagy inhibition is attenuated in FGF15‐null mice. Upon FGF19 treatment or feeding, SHP recruits LSD1 to CREB‐bound autophagy genes, including Tfeb, resulting in dissociation of CRTC2, LSD1‐mediated demethylation of gene‐activation histone marks H3K4‐me2/3, and subsequent accumulation of repressive histone modifications. Both FXR and SHP inhibit hepatic autophagy interdependently, but while FXR acts early, SHP acts relatively late after feeding, which effectively sustains postprandial inhibition of autophagy. This study demonstrates that the FGF19‐SHP‐LSD1 axis maintains homeostasis by suppressing unnecessary autophagic breakdown of cellular components, including lipids, under nutrient‐rich postprandial conditions.
Frank E. Jones - One of the best experts on this subject based on the ideXlab platform.
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jumonji arid1 b jarid1b protein promotes breast tumor cell cycle progression through Epigenetic Repression of microrna let 7e
Journal of Biological Chemistry, 2011Co-Authors: Doyel Mitra, Partha Das, Felicia C. Huynh, Frank E. JonesAbstract:MicroRNAs (miRs) function as tumor suppressors or oncogenes in multiple tumor types. Although miR expression is tightly regulated, the molecular basis of miR regulation is poorly understood. Here, we investigated the influence of the histone demethylase Jumonji/ARID1 B (JARID1B) on miR regulation in breast tumor cells. In MCF-7 cells with stable RNAi-mediated suppression of JARID1B expression we identified altered regulation of multiple miRs including let-7e, a member of the let-7 family of tumor suppressor miRs. Chromatin immunoprecipitation analysis demonstrated JARID1B binding to the let-7e promoter region as well as removal of the of H3K4me3 histone mark associated with active gene expression. These results suggest that JARID1B Epigenetically represses let-7e expression. JARID1B stimulates tumor cell proliferation by promoting the G1 to S transition. As predicted, suppression of JARID1B resulted in an accumulation of MCF-7 cells in G1. We confirmed that cyclin D1, which also promotes G1 progression, is a direct target of let-7e, and we show that cyclin D1 expression is suppressed in JARID1B knockdown cells. Cyclin D1 expression and cell cycle progression were restored following inhibition of let-7e, suggesting that JARID1B Repression of let-7e contributes to cyclin D1 expression and JARID1B-mediated cell cycle progression. Our results indicate that the JARID1B demethylase contributes to tumor cell proliferation through the Epigenetic Repression of a tumor suppressor miR.
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Jumonji/ARID1 B (JARID1B) protein promotes breast tumor cell cycle progression through Epigenetic Repression of microRNA let-7e.
The Journal of biological chemistry, 2011Co-Authors: Doyel Mitra, Partha Das, Felicia C. Huynh, Frank E. JonesAbstract:MicroRNAs (miRs) function as tumor suppressors or oncogenes in multiple tumor types. Although miR expression is tightly regulated, the molecular basis of miR regulation is poorly understood. Here, we investigated the influence of the histone demethylase Jumonji/ARID1 B (JARID1B) on miR regulation in breast tumor cells. In MCF-7 cells with stable RNAi-mediated suppression of JARID1B expression we identified altered regulation of multiple miRs including let-7e, a member of the let-7 family of tumor suppressor miRs. Chromatin immunoprecipitation analysis demonstrated JARID1B binding to the let-7e promoter region as well as removal of the of H3K4me3 histone mark associated with active gene expression. These results suggest that JARID1B Epigenetically represses let-7e expression. JARID1B stimulates tumor cell proliferation by promoting the G1 to S transition. As predicted, suppression of JARID1B resulted in an accumulation of MCF-7 cells in G1. We confirmed that cyclin D1, which also promotes G1 progression, is a direct target of let-7e, and we show that cyclin D1 expression is suppressed in JARID1B knockdown cells. Cyclin D1 expression and cell cycle progression were restored following inhibition of let-7e, suggesting that JARID1B Repression of let-7e contributes to cyclin D1 expression and JARID1B-mediated cell cycle progression. Our results indicate that the JARID1B demethylase contributes to tumor cell proliferation through the Epigenetic Repression of a tumor suppressor miR.
Thomas M. Kristie - One of the best experts on this subject based on the ideXlab platform.
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Epigenetic Repression of herpes simplex virus infection by the nucleosome remodeler chd3
Mbio, 2014Co-Authors: Jesse H. Arbuckle, Thomas M. KristieAbstract:ABSTRACT Upon infection, the genome of herpes simplex virus is rapidly incorporated into nucleosomes displaying histone modifications characteristic of heterochromatic structures. The initiation of infection requires complex viral-cellular interactions that ultimately circumvent this Repression by utilizing host cell enzymes to remove repressive histone marks and install those that promote viral gene expression. The reversion of Repression and activation of viral gene expression is mediated by the cellular coactivator HCF-1 in association with histone demethylases and methyltransferases. However, the mechanisms and the components that are involved in the initial Repression remain unclear. In this study, the chromatin remodeler chromodomain helicase DNA binding (CHD3) protein is identified as an important component of the initial Repression of the herpesvirus genome. CHD3 localizes to early viral foci and suppresses viral gene expression. Depletion of CHD3 results in enhanced viral immediate early gene expression and an increase in the number of transcriptionally active viral genomes in the cell. Importantly, CHD3 can recognize the repressive histone marks that have been detected in the chromatin associated with the viral genome and this remodeler is important for ultimately reducing the levels of accessible viral genomes. A model is presented in which CHD3 represses viral infection in opposition to the actions of the HCF-1 coactivator complex. This dynamic, at least in part, determines the initiation of viral infection. IMPORTANCE Chromatin modulation of herpesvirus infection is a dynamic process involving regulatory components that mediate suppression and those that promote viral gene expression and the progression of infection. The mechanisms by which the host cell employs the assembly and modulation of chromatin as an antiviral defense strategy against an invading herpesvirus remain unclear. This study defines a critical cellular component that mediates the initial Repression of infecting HSV genomes and contributes to understanding the dynamics of this complex interplay between host cell and viral pathogen.
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Epigenetic Repression of Herpes Simplex Virus Infection by the Nucleosome Remodeler CHD3
mBio, 2014Co-Authors: Jesse H. Arbuckle, Thomas M. KristieAbstract:Upon infection, the genome of herpes simplex virus is rapidly incorporated into nucleosomes displaying histone modifications characteristic of heterochromatic structures. The initiation of infection requires complex viral-cellular interactions that ultimately circumvent this Repression by utilizing host cell enzymes to remove repressive histone marks and install those that promote viral gene expression. The reversion of Repression and activation of viral gene expression is mediated by the cellular coactivator HCF-1 in association with histone demethylases and methyltransferases. However, the mechanisms and the components that are involved in the initial Repression remain unclear. In this study, the chromatin remodeler chromodomain helicase DNA binding (CHD3) protein is identified as an important component of the initial Repression of the herpesvirus genome. CHD3 localizes to early viral foci and suppresses viral gene expression. Depletion of CHD3 results in enhanced viral immediate early gene expression and an increase in the number of transcriptionally active viral genomes in the cell. Importantly, CHD3 can recognize the repressive histone marks that have been detected in the chromatin associated with the viral genome and this remodeler is important for ultimately reducing the levels of accessible viral genomes. A model is presented in which CHD3 represses viral infection in opposition to the actions of the HCF-1 coactivator complex. This dynamic, at least in part, determines the initiation of viral infection. Chromatin modulation of herpesvirus infection is a dynamic process involving regulatory components that mediate suppression and those that promote viral gene expression and the progression of infection. The mechanisms by which the host cell employs the assembly and modulation of chromatin as an antiviral defense strategy against an invading herpesvirus remain unclear. This study defines a critical cellular component that mediates the initial Repression of infecting HSV genomes and contributes to understanding the dynamics of this complex interplay between host cell and viral pathogen.