Nucleus (Austin, Tex.)Pub Date : 2018-01-01Epub Date: 2017-09-14DOI: 10.1080/19491034.2017.1361578
Fouziya R Shah, Younus A Bhat, Ajazul H Wani
{"title":"Subnuclear distribution of proteins: Links with genome architecture.","authors":"Fouziya R Shah, Younus A Bhat, Ajazul H Wani","doi":"10.1080/19491034.2017.1361578","DOIUrl":"10.1080/19491034.2017.1361578","url":null,"abstract":"<p><p>Metazoan genomes have a hierarchal 3-dimensional (3D) organization scaling from nucleosomes, loops, topologically associating domains (TADs), compartments, to chromosome territories. The 3D organization of genome has been linked with development, differentiation and disease. However, the principles governing the 3D chromatin architecture are just beginning to get unraveled. The nucleus has very high concentration of proteins and these proteins are either diffusely distributed throughout the nucleus, or aggregated in the form of foci/bodies/clusters/speckles or in combination of both. Several evidences suggest that the distribution of proteins within the nuclear space is linked to the organization and function of genome. Here, we describe advances made in understanding the relationship between subnuclear distribution of proteins and genome architecture.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":" ","pages":"42-55"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5973252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35408203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
G Peretto, S Sala, S Benedetti, C Di Resta, L Gigli, M Ferrari, P Della Bella
{"title":"Updated clinical overview on cardiac laminopathies: an electrical and mechanical disease.","authors":"G Peretto, S Sala, S Benedetti, C Di Resta, L Gigli, M Ferrari, P Della Bella","doi":"10.1080/19491034.2018.1489195","DOIUrl":"10.1080/19491034.2018.1489195","url":null,"abstract":"<p><p>Cardiac laminopathies, associated with mutations in the LMNA gene, encompass a wide spectrum of clinical manifestations, involving electrical and mechanical alterations of cardiomyocytes. Thus, dilated cardiomyopathy, bradyarrhythmias and atrial or ventricular tachyarrhythmias may occur in a number of combined phenotypes. Nowadays, some attempt has been made to identify clinical predictors for the most life-threatening complications of LMNA-associated heart disease, i.e. sudden cardiac death and end-stage heart failure. The goal of this manuscript is to combine the most recent evidences in an updated review to show the state-of-the-art of such a complex disease group. This is supposed to be the starting point to collect more data and design new ad hoc studies to identify clinically useful predictors to stratify risk in mutation carriers, including probands and their asymptomatic relatives.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":" ","pages":"380-391"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19491034.2018.1489195","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36246442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Polycystic ovary syndrome in familial partial lipodystrophy type 2 (FPLD2): basic and clinical aspects.","authors":"Alessandra Gambineri, Laura Zanotti","doi":"10.1080/19491034.2018.1509659","DOIUrl":"https://doi.org/10.1080/19491034.2018.1509659","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is a common disorder with a high phenotypic variability. Frequently, it is associated with a mild to moderate insulin resistance (IR) caused by an interaction between polygenic diathesis and the environment. However, PCOS may be a complication of an underlying syndrome of severe IR such as insulin receptor autoantibodies, mutations in the insulin receptor or in the signalling pathway downstream from the insulin receptor or, most frequently, a defect in function or in the development of the subcutaneous adipose tissue. Such conditions are clinically characterized by lipodystrophy. Lipodystrophy in some cases is produced by a single-gene defect. In our experience, PCOS secondary to a missense mutation in the LMNA gene, known as familial partial lipodystrophy type 2 (FPLD2), is the most frequent form of PCOS secondary to severe IR due to genetically determined lipodystrophy. These forms should be identified as they benefit from tailored therapies.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":" ","pages":"392-397"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19491034.2018.1509659","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36415700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nucleus (Austin, Tex.)Pub Date : 2018-01-01Epub Date: 2017-11-13DOI: 10.1080/19491034.2017.1371398
Su-Jin Heo, Brian D Cosgrove, Eric N Dai, Robert L Mauck
{"title":"Mechano-adaptation of the stem cell nucleus.","authors":"Su-Jin Heo, Brian D Cosgrove, Eric N Dai, Robert L Mauck","doi":"10.1080/19491034.2017.1371398","DOIUrl":"https://doi.org/10.1080/19491034.2017.1371398","url":null,"abstract":"<p><p>Exogenous mechanical forces are transmitted through the cell and to the nucleus, initiating mechanotransductive signaling cascades with profound effects on cellular function and stem cell fate. A growing body of evidence has shown that the force sensing and force-responsive elements of the nucleus adapt to these mechanotransductive events, tuning their response to future mechanical input. The mechanisms underlying this \"mechano-adaptation\" are only just beginning to be elucidated, and it remains poorly understood how these components act and adapt in tandem to drive stem cell differentiation. Here, we review the evidence on how the stem cell nucleus responds and adapts to physical forces, and provide a perspective on how this mechano-adaptation may function to drive and enforce stem cell differentiation.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":" ","pages":"9-19"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19491034.2017.1371398","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35571870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C A Brackley, J Johnson, D Michieletto, A N Morozov, M Nicodemi, P R Cook, D Marenduzzo
{"title":"Extrusion without a motor: a new take on the loop extrusion model of genome organization.","authors":"C A Brackley, J Johnson, D Michieletto, A N Morozov, M Nicodemi, P R Cook, D Marenduzzo","doi":"10.1080/19491034.2017.1421825","DOIUrl":"10.1080/19491034.2017.1421825","url":null,"abstract":"<p><p>Chromatin loop extrusion is a popular model for the formation of CTCF loops and topological domains. Recent HiC data have revealed a strong bias in favour of a particular arrangement of the CTCF binding motifs that stabilize loops, and extrusion is the only model to date which can explain this. However, the model requires a motor to generate the loops, and although cohesin is a strong candidate for the extruding factor, a suitable motor protein (or a motor activity in cohesin itself) has yet to be found. Here we explore a new hypothesis: that there is no motor, and thermal motion within the nucleus drives extrusion. Using theoretical modelling and computer simulations we ask whether such diffusive extrusion could feasibly generate loops. Our simulations uncover an interesting ratchet effect (where an osmotic pressure promotes loop growth), and suggest, by comparison to recent in vitro and in vivo measurements, that diffusive extrusion can in principle generate loops of the size observed in the data. Extra View on : C. A. Brackley, J. Johnson, D. Michieletto, A. N. Morozov, M. Nicodemi, P. R. Cook, and D. Marenduzzo \"Non-equilibrium chromosome looping via molecular slip-links\", Physical Review Letters 119 138101 (2017).</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":" ","pages":"95-103"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9a/cc/kncl-09-01-1421825.PMC5973195.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35707134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lukasz Majewski, Jolanta Nowak, Magdalena Sobczak, Olena Karatsai, Serhiy Havrylov, Robert Lenartowski, Malgorzata Suszek, Marta Lenartowska, Maria Jolanta Redowicz
{"title":"Myosin VI in the nucleus of neurosecretory PC12 cells: Stimulation-dependent nuclear translocation and interaction with nuclear proteins.","authors":"Lukasz Majewski, Jolanta Nowak, Magdalena Sobczak, Olena Karatsai, Serhiy Havrylov, Robert Lenartowski, Malgorzata Suszek, Marta Lenartowska, Maria Jolanta Redowicz","doi":"10.1080/19491034.2017.1421881","DOIUrl":"10.1080/19491034.2017.1421881","url":null,"abstract":"<p><p>Myosin VI (MVI) is a unique actin-based motor protein moving towards the minus end of actin filaments, in the opposite direction than other known myosins. Besides well described functions of MVI in endocytosis and maintenance of Golgi apparatus, there are few reports showing its involvement in transcription. We previously demonstrated that in neurosecretory PC12 cells MVI was present in the cytoplasm and nucleus, and its depletion caused substantial inhibition of cell migration and proliferation. Here, we show an increase in nuclear localization of MVI upon cell stimulation, and identification of potential nuclear localization (NLS) and nuclear export (NES) signals within MVI heavy chain. These signals seem to be functional as the MVI nuclear presence was affected by the inhibitors of nuclear import (ivermectin) and export (leptomycin B). In nuclei of stimulated cells, MVI colocalized with active RNA polymerase II, BrUTP-containing transcription sites and transcription factor SP1 as well as SC35 and PML proteins, markers of nuclear speckles and PML bodies, respectively. Mass spectrometry analysis of samples of a GST-pull-down assay with the MVI tail domain as a \"bait\" identified several new potential MVI binding partners. Among them are proteins involved in transcription and post-transcriptional processes. We confirmed interaction of MVI with heterogeneous nuclear ribonucleoprotein U (hnRNPU) and nucleolin, proteins involved in pre-mRNA binding and transport, and nucleolar function, respectively. Our data provide an insight into mechanisms of involvement of MVI in nuclear processes via interaction with nuclear proteins and support a notion for important role(s) for MVI in gene expression.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":" ","pages":"125-141"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5973263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35701153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Differential staining of peripheral nuclear chromatin with Acridine orange implies an A-form epichromatin conformation of the DNA.","authors":"Jekaterina Erenpreisa, Jekabs Krigerts, Kristine Salmina, Turs Selga, Hermanis Sorokins, Talivaldis Freivalds","doi":"10.1080/19491034.2018.1431081","DOIUrl":"https://doi.org/10.1080/19491034.2018.1431081","url":null,"abstract":"<p><p>The chromatin observed by conventional electron microscopy under the nuclear envelope constitutes a single layer of dense 30-35 nm granules, while ∼30 nm fibrils laterally attached to them, form large patches of lamin-associated domains (LADs). This particular surface \"epichromatin\" can be discerned by specific (H2A+H2B+DNA) conformational antibody at the inner nuclear envelope and around mitotic chromosomes. In order to differentiate the DNA conformation of the peripheral chromatin we applied an Acridine orange (AO) DNA structural test involving RNAse treatment and the addition of AO after acid pre-treatment. MCF-7 cells treated in this way revealed yellow/red patches of LADs attached to a thin green nuclear rim and with mitotic chromosomes outlined in green, topologically corresponding to epichromatin epitope staining by immunofluorescence. Differentially from LADs, the epichromatin was unable to provide metachromatic staining by AO, unless thermally denatured at 94<sup>o</sup>C. DNA enrichment in GC stretches has been recently reported for immunoprecipitated ∼ 1Kb epichromatin domains. Together these data suggest that certain epichromatin segments assume the relatively hydrophobic DNA A-conformation at the nuclear envelope and surface of mitotic chromosomes, preventing AO side dimerisation. We hypothesize that epichromatin domains form nucleosome superbeads. Hydrophobic interactions stack these superbeads and align them at the nuclear envelope, while repulsing the hydrophilic LADs. The hydrophobicity of epichromatin explains its location at the surface of mitotic chromosomes and its function in mediating chromosome attachment to the restituting nuclear envelope during telophase.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":" ","pages":"171-181"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19491034.2018.1431081","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35761772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"From dynamic chromatin architecture to DNA damage repair and back.","authors":"Emmanuelle Fabre, Christophe Zimmer","doi":"10.1080/19491034.2017.1419847","DOIUrl":"https://doi.org/10.1080/19491034.2017.1419847","url":null,"abstract":"<p><p>Maintaining the integrity of the genome in the face of DNA damage is crucial to ensure the survival of the cell and normal development. DNA lesions and repair occur in the context of the chromatin fiber, whose 3D organization and movements in the restricted volume of the nucleus are under intense scrutiny. Here, we highlight work from our and other labs that addresses how the dynamic organization of the chromatin fiber affects the repair of damaged DNA and how, conversely, DNA damage and repair affect the structure and dynamics of chromatin in the budding yeast nucleus.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":" ","pages":"161-170"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19491034.2017.1419847","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35683031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Invertebrate models of lamin diseases.","authors":"Ryszard Rzepecki, Yosef Gruenbaum","doi":"10.1080/19491034.2018.1454166","DOIUrl":"https://doi.org/10.1080/19491034.2018.1454166","url":null,"abstract":"<p><p>Lamins are evolutionarily conserved nuclear intermediate filament proteins. They provide structural support for the nucleus and help regulate many other nuclear activities. Mutations in human lamin genes, and especially in the LMNA gene, cause numerous diseases, termed laminopathies, including muscle, cardiac, metabolic, neuronal and early aging diseases. Most laminopathies arise from autosomal dominant missense mutations. Many of the mutant residues are conserved in the lamin genes of the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster. Our current understanding of the mechanisms leading to these diseases is mostly based on patients cell lines and animal models including C. elegans and D. melanogaster. The simpler lamin system and the powerful genetic tools offered by these invertebrate organisms greatly contributed to such studies. Here we provide an overview of the studies of laminopathies in Drosophila and C. elegans models.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":" ","pages":"227-234"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19491034.2018.1454166","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35930783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Charlotte Capitanchik, Charles R Dixon, Selene K Swanson, Laurence Florens, Alastair R W Kerr, Eric C Schirmer
{"title":"Analysis of RNA-Seq datasets reveals enrichment of tissue-specific splice variants for nuclear envelope proteins.","authors":"Charlotte Capitanchik, Charles R Dixon, Selene K Swanson, Laurence Florens, Alastair R W Kerr, Eric C Schirmer","doi":"10.1080/19491034.2018.1469351","DOIUrl":"10.1080/19491034.2018.1469351","url":null,"abstract":"<p><p>Laminopathies yield tissue-specific pathologies, yet arise from mutation of ubiquitously-expressed genes. A little investigated hypothesis to explain this is that the mutated proteins or their partners have tissue-specific splice variants. To test this, we analyzed RNA-Seq datasets, finding novel isoforms or isoform tissue-specificity for: Lap2, linked to cardiomyopathy; Nesprin 2, linked to Emery-Dreifuss muscular dystrophy and Lmo7, that regulates the Emery-Dreifuss muscular dystrophy linked emerin gene. Interestingly, the muscle-specific Lmo7 exon is rich in serine phosphorylation motifs, suggesting regulatory function. Muscle-specific splice variants in non-nuclear envelope proteins linked to other muscular dystrophies were also found. Nucleoporins tissue-specific variants were found for Nup54, Nup133, Nup153 and Nup358/RanBP2. RT-PCR confirmed novel Lmo7 and RanBP2 variants and specific knockdown of the Lmo7 variantreduced myogenic index. Nuclear envelope proteins were enriched for tissue-specific splice variants compared to the rest of the genome, suggesting that splice variants contribute to its tissue-specific functions.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":" ","pages":"410-430"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7000147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36232086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}