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  • 1
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    Haematopoietic malignancies caused by dysregulation of a chromatin-binding PHD finger (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-05-12
    Description: Histone H3 lysine 4 methylation (H3K4me) has been proposed as a critical component in regulating gene expression, epigenetic states, and cellular identities1. The biological meaning of H3K4me is interpreted by conserved modules including plant homeodomain (PHD) fingers that recognize varied H3K4me states. The dysregulation of PHD fingers has been implicated in several human diseases, including cancers and immune or neurological disorders. Here we report that fusing an H3K4-trimethylation (H3K4me3)-binding PHD finger, such as the carboxy-terminal PHD finger of PHF23 or JARID1A (also known as KDM5A or RBBP2), to a common fusion partner nucleoporin-98 (NUP98) as identified in human leukaemias, generated potent oncoproteins that arrested haematopoietic differentiation and induced acute myeloid leukaemia in murine models. In these processes, a PHD finger that specifically recognizes H3K4me3/2 marks was essential for leukaemogenesis. Mutations in PHD fingers that abrogated H3K4me3 binding also abolished leukaemic transformation. NUP98-PHD fusion prevented the differentiation-associated removal of H3K4me3 at many loci encoding lineage-specific transcription factors (Hox(s), Gata3, Meis1, Eya1 and Pbx1), and enforced their active gene transcription in murine haematopoietic stem/progenitor cells. Mechanistically, NUP98-PHD fusions act as 'chromatin boundary factors', dominating over polycomb-mediated gene silencing to 'lock' developmentally critical loci into an active chromatin state (H3K4me3 with induced histone acetylation), a state that defined leukaemia stem cells. Collectively, our studies represent, to our knowledge, the first report that deregulation of the PHD finger, an 'effector' of specific histone modification, perturbs the epigenetic dynamics on developmentally critical loci, catastrophizes cellular fate decision-making, and even causes oncogenesis during mammalian development.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2697266/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2697266/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Gang G -- Song, Jikui -- Wang, Zhanxin -- Dormann, Holger L -- Casadio, Fabio -- Li, Haitao -- Luo, Jun-Li -- Patel, Dinshaw J -- Allis, C David -- K99 CA151683/CA/NCI NIH HHS/ -- R37 GM053512/GM/NIGMS NIH HHS/ -- R37 GM053512-30/GM/NIGMS NIH HHS/ -- England -- Nature. 2009 Jun 11;459(7248):847-51. doi: 10.1038/nature08036.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Chromatin Biology & Epigenetics, The Rockefeller University, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19430464" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs/genetics/physiology ; Animals ; Cell Transformation, Neoplastic ; Cells, Cultured ; Chromatin/*metabolism ; Epigenesis, Genetic ; Gene Expression Regulation, Developmental ; Genes, Homeobox/genetics ; Hematologic Neoplasms/genetics/*metabolism/*pathology ; Hematopoiesis/genetics ; Hematopoietic Stem Cells/metabolism/pathology ; Histones/chemistry/metabolism ; Humans ; Intracellular Signaling Peptides and Proteins/*chemistry/genetics/*metabolism ; Lysine/metabolism ; Magnetic Resonance Spectroscopy ; Methylation ; Mice ; Models, Molecular ; Nuclear Pore Complex Proteins/chemistry/genetics/metabolism ; Oncogene Proteins, Fusion/*chemistry/genetics/*metabolism ; Protein Binding ; Protein Conformation ; Retinoblastoma-Binding Protein 2 ; Transcription, Genetic ; Tumor Suppressor Proteins/*chemistry/genetics/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    Metamorphic fluid superimposition of the Changba-Lijiagou Pb-Zn deposit, West Qinling Orogen, central China (2018)
    Geological Society of London
    Details
    Publication Date: 2018
    Description: 〈p〉Several large to giant Pb–Zn deposits in the West Qinling Orogen in central China are argued to be of SEDEX (sedimentary exhalative) type or of epigenetic hydrothermal type. Additionally, the nature of the mineralizing fluids is poorly known. Our observations suggest that early stage primary marine sedimentary mineralization is characterized by laminated or disseminated fine-grained massive sulphide ores, and late stage metamorphic superimposition is represented by coarser equigranular annealed textures and the disruption of thinly laminated structures. Three coexisting types of fluid inclusions were recognized: H〈sub〉2〈/sub〉O–NaCl (type I); H〈sub〉2〈/sub〉O–NaCl–CH〈sub〉4〈/sub〉–CO〈sub〉2〈/sub〉 (type II); and CH〈sub〉4〈/sub〉–CO〈sub〉2〈/sub〉 (type III). The coexisting type I and II inclusions show similar homogenization temperature values but different salinities, indicating that fluid immiscibility occurred. Formation pressures calculated using type III inclusions are high (72.5–174.5 MPa). The lead isotopes of the sulphides and calcites show a narrow range. The primary sedimentary ore textures plus the similar lead isotopes between the ores and the wall rocks suggest a SEDEX origin, but the annealed recrystallization textures, the immiscible carbonic fluid inclusion assemblages and higher formation pressures suggest a strong late-stage metamorphic superimposition on the original SEDEX-type ores.〈/p〉
    Print ISSN: 0375-6440
    Electronic ISSN: 2041-4927
    Topics: Geosciences
    Published by Geological Society of London
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  • 3
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    Geology, fluid inclusion, and isotope constraints on ore genesis of the Neoproterozoic Jinshan orogenic gold deposit, South China (2013)
    Wiley
    In: Geofluids
    Details
    Publication Date: 2013-07-25
    Description: The Jinshan gold deposit is located in the Neoproterozoic Jiangnan orogen between the Yangtze and Cathaysia blocks. Gold-bearing disseminated ores are associated with the earlier stage of NWW-trending ductile zone, and auriferous quartz vein-type ores show an intimate relationship with the later stage of NE-trending brittle-ductile zones. Fluid-inclusion studies were conducted on the quartz veins. Three types of fluid inclusions can be identified: H 2 O–CO 2 inclusions (type I), CO 2 -rich inclusions (type II), and aqueous inclusions (type III). The pre-ore stage, quartz-pyrite veins primarily contain type I inclusions with constant CO 2 bubble volumetric proportions. The main gold mineralization-stage veins have all three types of inclusions with variable gas-phase ratios and CO 2 contents. The post-ore stage carbonate±chlorite veinlets only contain type III inclusions. Type I inclusions in the pre-ore stage display homogenization temperatures (Th) of 285–340°C, with salinities of 1.4–6.1 wt.% NaCl equivalent. In the main gold mineralization stage, type II and III inclusions show similar Th at 208–277°C, but contrasting salinity values with 0.6–3.6 and 3.5–8.9 wt.% NaCl equivalent, and type I inclusions show variable CO 2 -phase proportions and have Th of 241–292°C and salinities of 1.0–7.0 wt.% NaCl equivalent. In the post-ore stage, type III inclusions yield Th of 109–201°C and salinities of 1.1–6.4 wt.% NaCl equivalent. Petrological observations and microthermometric results show that fluid immiscibility primarily occurred during the gold mineralization stages. The oxygen and hydrogen isotope compositions (δ 18 O   = +6.9‰ to +11.2‰, δD = −71‰ to −46‰) of inclusion water in quartz grains imply that ore fluids were principally metamorphic in origin. The sulfur and lead values of sulfide from the ores are analogous to those from the basement strata, suggesting a predominantly crustal source of the ore sulfides. The Jinshan deposit is a typical orogenic gold deposit. Ore fluids are low salinity, moderate temperatures and CO 2 rich. Fluid immiscibility takes place during the ore formation process. Hydrogen, oxygen, sulfur and lead isotopes suggest that ore fluids and materials are metamorphic origin. The Jinshan deposit is a typical Neoproterozoic orogenic gold deposit in the East Jiangnan orogen.
    Print ISSN: 1468-8115
    Electronic ISSN: 1468-8123
    Topics: Geosciences
    Published by Wiley
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  • 4
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    Metamorphic fluid superimposition of the Changba-Lijiagou Pb-Zn deposit, West Qinling Orogen, central China (2018)
    Geological Society (of London)
    Details
    Publication Date: 2018-05-23
    Description: Several large to giant Pb–Zn deposits in the West Qinling Orogen in central China are argued to be of SEDEX (sedimentary exhalative) type or of epigenetic hydrothermal type. Additionally, the nature of the mineralizing fluids is poorly known. Our observations suggest that early stage primary marine sedimentary mineralization is characterized by laminated or disseminated fine-grained massive sulphide ores, and late stage metamorphic superimposition is represented by coarser equigranular annealed textures and the disruption of thinly laminated structures. Three coexisting types of fluid inclusions were recognized: H 2 O–NaCl (type I); H 2 O–NaCl–CH 4 –CO 2 (type II); and CH 4 –CO 2 (type III). The coexisting type I and II inclusions show similar homogenization temperature values but different salinities, indicating that fluid immiscibility occurred. Formation pressures calculated using type III inclusions are high (72.5–174.5 MPa). The lead isotopes of the sulphides and calcites show a narrow range. The primary sedimentary ore textures plus the similar lead isotopes between the ores and the wall rocks suggest a SEDEX origin, but the annealed recrystallization textures, the immiscible carbonic fluid inclusion assemblages and higher formation pressures suggest a strong late-stage metamorphic superimposition on the original SEDEX-type ores.
    Print ISSN: 0305-8719
    Electronic ISSN: 2041-4927
    Topics: Geosciences
    Published by Geological Society (of London)
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  • 5
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    CaMKK{beta} phosphorylation of SIRT1 [Physiology] (2013)
    National Academy of Sciences
    Details
    Publication Date: 2013-06-26
    Description: Atheroprotective flow exerts antioxidative and anti-inflammatory effects on vascular endothelial cells (ECs), in part through the induction of Sirtuin 1 (SIRT1), a class III histone deacetylase. The role of Ca2+/calmodulin-dependent protein kinase kinase (CaMKK)β in flow induction of SIRT1 both in vitro and in vivo was investigated. Pulsatile shear stress...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 6
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    Lens epithelium-derived growth factor fusion proteins redirect HIV-1 DNA integration (2010)
    National Academy of Sciences
    Details
    Publication Date: 2010-02-01
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 7
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    GPU MrBayes V3.1: MrBayes on Graphics Processing Units for Protein Sequence Data (2015)
    Oxford University Press
    Details
    Publication Date: 2015-08-20
    Description: We present a modified GPU (graphics processing unit) version of MrBayes, called ta(MC) 3 (GPU MrBayes V3.1), for Bayesian phylogenetic inference on protein data sets. Our main contributions are 1) utilizing 64-bit variables, thereby enabling ta(MC) 3 to process larger data sets than MrBayes; and 2) to use Kahan summation to improve accuracy, convergence rates, and consequently runtime. Versus the current fastest software, we achieve a speedup of up to around 2.5 (and up to around 90 vs. serial MrBayes), and more on multi-GPU hardware. GPU MrBayes V3.1 is available from http://sourceforge.net/projects/mrbayes-gpu/ .
    Print ISSN: 0737-4038
    Electronic ISSN: 1537-1719
    Topics: Biology
    Published by Oxford University Press
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  • 8
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    Functional characterization of INS in Arabidopsis [Plant Biology] (2015)
    National Academy of Sciences
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    Publication Date: 2015-04-15
    Description: The phytohormone auxin regulates nearly all aspects of plant growth and development. Tremendous achievements have been made in elucidating the tryptophan (Trp)-dependent auxin biosynthetic pathway; however, the genetic evidence, key components, and functions of the Trp-independent pathway remain elusive. Here we report that the Arabidopsis indole synthase mutant is defective...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 9
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    Nucleolar stress and impaired stress granule formation contribute to C9orf72 RAN translation-induced cytotoxicity (2015)
    Oxford University Press
    Details
    Publication Date: 2015-04-04
    Description: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are the two common neurodegenerative diseases that have been associated with the GGGGCC·GGCCCC repeat RNA expansion in a noncoding region of C9orf72 . It has been previously reported that unconventional repeat-associated non-ATG (RAN) translation of GGGGCC·GGCCCC repeats produces five types of dipeptide-repeat proteins (referred to as RAN proteins): poly-glycine-alanine (GA), poly-glycine-proline (GP), poly-glycine-arginine (GR), poly-proline-arginine (PR) and poly-proline-alanine (PA). Although protein aggregates of RAN proteins have been found in patients, it is unclear whether RAN protein aggregation induces neurotoxicity. In the present study, we aimed to understand the biological properties of all five types of RAN proteins. Surprisingly, our results showed that none of these RAN proteins was aggregate-prone in our cellular model and that the turnover of these RAN proteins was not affected by the ubiquitin–proteasome system or autophagy. Moreover, poly-GR and poly-PR, but not poly-GA, poly-GP or poly-PA, localized to the nucleolus and induced the translocation of the key nucleolar component nucleophosmin, leading to nucleolar stress and cell death. This poly-GR- and poly-PR-mediated defect in nucleolar function was associated with the suppression of ribosomal RNA synthesis and the impairment of stress granule formation. Taken together, the results of the present study suggest a simple model of the molecular mechanisms underlying RAN translation-mediated cytotoxicity in C9orf72 -linked ALS/FTD in which nucleolar stress, but not protein aggregation, is the primary contributor to C9orf72 -linked neurodegeneration.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 10
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    Relationship between Maceral of Coal and Coal-bed Methane adsorption ability in Sihe Coalmine of Qinshui Basin, China (2018)
    Institute of Physics (IOP)
    Details
    Publication Date: 2018-05-17
    Description: Maceral components and its content of coal were divided based on the microscopic characteristics of coal. The Langmuir volume and the Langmuir pressure were tested, and the Langmuir volume represents the adsorption capacity of coal. The formation of coal bed methane is affected by the partition of the maceral components in coal. Therefore, the relationship between maceral composition and coal bed methane adsorption capacity of coal was analyzed. The results show that the maceral components of coal are dominated by vitrinite and inertinite in the study area, and the content of inertinite is below 32%. The vitrinite group has a negative linear correlation with the Langmuir volume, and the inertia composition has a positive linear correlation with it. The cellular structures in the inertinite are the main site of coal bed methane enrichment. The microstructure of coal affects the coalbed methane content and the stage of hydrocarbon generation in coal. This indicates that the micros...
    Print ISSN: 1757-8981
    Electronic ISSN: 1757-899X
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Published by Institute of Physics (IOP)
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