{"title":"The coordination of nuclear envelope assembly and chromosome segregation in metazoans.","authors":"Shiwei Liu, David Pellman","doi":"10.1080/19491034.2020.1742064","DOIUrl":"10.1080/19491034.2020.1742064","url":null,"abstract":"<p><p>The nuclear envelope (NE) is composed of two lipid bilayer membranes that enclose the eukaryotic genome. In interphase, the NE is perforated by thousands of nuclear pore complexes (NPCs), which allow transport in and out of the nucleus. During mitosis in metazoans, the NE is broken down and then reassembled in a manner that enables proper chromosome segregation and the formation of a single nucleus in each daughter cell. Defects in coordinating NE reformation and chromosome segregation can cause aberrant nuclear architecture. This includes the formation of micronuclei, which can trigger a catastrophic mutational process commonly observed in cancers called chromothripsis. Here, we discuss the current understanding of the coordination of NE reformation with chromosome segregation during mitotic exit in metazoans. We review differing models in the field and highlight recent work suggesting that normal NE reformation and chromosome segregation are physically linked through the timing of mitotic spindle disassembly.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":"11 1","pages":"35-52"},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37768740","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}
Matthew S Nord, Cyril Bernis, Sarah Carmona, Dennis C Garland, Anna Travesa, Douglass J Forbes
{"title":"Exportins can inhibit major mitotic assembly events <i>in vitro</i>: membrane fusion, nuclear pore formation, and spindle assembly.","authors":"Matthew S Nord, Cyril Bernis, Sarah Carmona, Dennis C Garland, Anna Travesa, Douglass J Forbes","doi":"10.1080/19491034.2020.1798093","DOIUrl":"https://doi.org/10.1080/19491034.2020.1798093","url":null,"abstract":"<p><strong>Xenopus: </strong>egg extracts are a powerful <i>in vitro</i> tool for studying complex biological processes, including nuclear reconstitution, nuclear membrane and pore assembly, and spindle assembly. Extracts have been further used to demonstrate a moonlighting regulatory role for nuclear import receptors or <i>importins</i> on these cell cycle assembly events. Here we show that <i>exportins</i> can also play a role in these events. Addition of Crm1, Exportin-t, or Exportin-5 decreased nuclear pore assembly in vitro. RanQ69L-GTP, a constitutively active form of RanGTP, ameliorated inhibition. Both Crm1 and Exportin-t inhibited fusion of nuclear membranes, again counteracted by RanQ69L-GTP. In mitotic extracts, Crm1 and Exportin-t negatively impacted spindle assembly. Pulldowns from the extracts using Crm1- or Exportin-t-beads revealed nucleoporins known to be essential for both nuclear pore and spindle assembly, with RanQ69L-GTP decreasing a subset of these target interactions. This study suggests a model where exportins, like importins, can regulate major mitotic assembly events.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":"11 1","pages":"178-193"},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19491034.2020.1798093","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38245606","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":"SATB1-mediated chromatin landscape in T cells.","authors":"Tomas Zelenka, Charalampos Spilianakis","doi":"10.1080/19491034.2020.1775037","DOIUrl":"https://doi.org/10.1080/19491034.2020.1775037","url":null,"abstract":"<p><p>The regulatory circuits that define developmental decisions of thymocytes are still incompletely resolved. SATB1 protein is predominantly expressed at the CD4<sup>+</sup>CD8<sup>+</sup>cell stage exerting its broad transcription regulation potential with both activatory and repressive roles. A series of post-translational modifications and the presence of potential SATB1 protein isoforms indicate the complexity of its regulatory potential. The most apparent mechanism of its involvement in gene expression regulation is via the orchestration of long-range chromatin loops between genes and their regulatory elements. Multiple SATB1 perturbations in mice uncovered a link to autoimmune diseases while clinical investigations on cancer research uncovered that SATB1 has a promoting role in several types of cancer and can be used as a prognostic biomarker. SATB1 is a multivalent tissue-specific factor with a broad and yet undetermined regulatory potential. Future investigations on this protein could further uncover T cell-specific regulatory pathways and link them to (patho)physiology.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":"11 1","pages":"117-131"},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19491034.2020.1775037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39094184","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}
Natalie Y Chen, Paul H Kim, Loren G Fong, Stephen G Young
{"title":"Nuclear membrane ruptures, cell death, and tissue damage in the setting of nuclear lamin deficiencies.","authors":"Natalie Y Chen, Paul H Kim, Loren G Fong, Stephen G Young","doi":"10.1080/19491034.2020.1815410","DOIUrl":"10.1080/19491034.2020.1815410","url":null,"abstract":"<p><p>The nuclear membranes function as a barrier to separate the cell nucleus from the cytoplasm, but this barrier can be compromised by nuclear membrane ruptures, leading to intermixing of nuclear and cytoplasmic contents. Spontaneous nuclear membrane ruptures (<i>i.e</i>., ruptures occurring in the absence of mechanical stress) have been observed in cultured cells, but they are more frequent in the setting of defects or deficiencies in nuclear lamins and when cells are subjected to mechanical stress. Nuclear membrane ruptures in cultured cells have been linked to DNA damage, but the relevance of ruptures to developmental or physiologic processes <i>in vivo</i> has received little attention. Recently, we addressed that issue by examining neuronal migration in the cerebral cortex, a developmental process that subjects the cell nucleus to mechanical stress. In the setting of lamin B1 deficiency, we observed frequent nuclear membrane ruptures in migrating neurons in the developing cerebral cortex and showed that those ruptures are likely the cause of observed DNA damage, neuronal cell death, and profound neuropathology. In this review, we discuss the physiologic relevance of nuclear membrane ruptures, with a focus on migrating neurons in cell culture and in the cerebral cortex of genetically modified mice.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":"11 1","pages":"237-249"},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19491034.2020.1815410","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38365679","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}
Xin Xie, S Raza Mahmood, Tamara Gjorgjieva, Piergiorgio Percipalle
{"title":"Emerging roles of cytoskeletal proteins in regulating gene expression and genome organization during differentiation.","authors":"Xin Xie, S Raza Mahmood, Tamara Gjorgjieva, Piergiorgio Percipalle","doi":"10.1080/19491034.2020.1742066","DOIUrl":"https://doi.org/10.1080/19491034.2020.1742066","url":null,"abstract":"<p><p>In the eukaryotic cell nucleus, cytoskeletal proteins are emerging as essential players in nuclear function. In particular, actin regulates chromatin as part of ATP-dependent chromatin remodeling complexes, it modulates transcription and it is incorporated into nascent ribonucleoprotein complexes, accompanying them from the site of transcription to polyribosomes. The nuclear actin pool is undistinguishable from the cytoplasmic one in terms of its ability to undergo polymerization and it has also been implicated in the dynamics of chromatin, regulating heterochromatin segregation at the nuclear lamina and maintaining heterochromatin levels in the nuclear interiors. One of the next frontiers is, therefore, to determine a possible involvement of nuclear actin in the functional architecture of the cell nucleus by regulating the hierarchical organization of chromatin and, thus, genome organization. Here, we discuss the repertoire of these potential actin functions and how they are likely to play a role in the context of cellular differentiation.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":"11 1","pages":"53-65"},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19491034.2020.1742066","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37771241","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":"Nuclear filaments: role in chromosomal positioning and gene expression.","authors":"Manindra Bera, Kaushik Sengupta","doi":"10.1080/19491034.2020.1769445","DOIUrl":"https://doi.org/10.1080/19491034.2020.1769445","url":null,"abstract":"ABSTRACT Nuclear lamins form an elastic meshwork underlying the inner nuclear membrane and provide mechanical rigidity to the nucleus and maintain shape. Lamins also maintain chromosome positioning and play important roles in several nuclear processes like replication, DNA damage repair, transcription, and epigenetic modifications. LMNA mutations affect cardiac tissue, muscle tissues, adipose tissues to precipitate several diseases collectively termed as laminopathies. However, the rationale behind LMNA mutations and laminopathies continues to elude scientists. During interphase, several chromosomes form inter/intrachromosomal contacts inside nucleoplasm and several chromosomal loops also stretch out to make a ‘loop-cluster’ which are key players to regulate gene expressions. In this perspective, we have proposed that the lamin network in tandem with nuclear actin and myosin provide mechanical rigidity to the chromosomal contacts and facilitate loop-clusters movements. LMNA mutations thus might perturb the landscape of chromosomal contacts or loop-clusters positioning which can impair gene expression profile.","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":"11 1","pages":"99-110"},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19491034.2020.1769445","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37976523","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}
Ada L Olins, Travis J Gould, Logan Boyd, Bettina Sarg, Donald E Olins
{"title":"Hyperosmotic stress: <i>in situ</i> chromatin phase separation.","authors":"Ada L Olins, Travis J Gould, Logan Boyd, Bettina Sarg, Donald E Olins","doi":"10.1080/19491034.2019.1710321","DOIUrl":"https://doi.org/10.1080/19491034.2019.1710321","url":null,"abstract":"<p><p>Dehydration of cells by acute hyperosmotic stress has profound effects upon cell structure and function. Interphase chromatin and mitotic chromosomes collapse (\"congelation\"). HL-60/S4 cells remain ~100% viable for, at least, 1 hour, exhibiting shrinkage to ~2/3 their original volume, when placed in 300mM sucrose in tissue culture medium. Fixed cells were imaged by immunostaining confocal and STED microscopy. At a \"global\" structural level (μm), mitotic chromosomes congeal into a residual gel with apparent (phase) separations of Ki67, CTCF, SMC2, RAD21, H1 histones and HMG proteins. At an \"intermediate\" level (sub-μm), radial distribution analysis of STED images revealed a most probable peak DNA density separation of ~0.16 μm, essentially unchanged by hyperosmotic stress. At a \"local\" structural level (~1-2 nm), in vivo crosslinking revealed essentially unchanged crosslinked products between H1, HMG and inner histones. Hyperosmotic cellular stress is discussed in terms of concepts of mitotic chromosome structure and liquid-liquid phase separation.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":"11 1","pages":"1-18"},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19491034.2019.1710321","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37531731","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}
Norman Reid Groves, Alecia Biel, Morgan Moser, Tyler Mendes, Katelyn Amstutz, Iris Meier
{"title":"Recent advances in understanding the biological roles of the plant nuclear envelope.","authors":"Norman Reid Groves, Alecia Biel, Morgan Moser, Tyler Mendes, Katelyn Amstutz, Iris Meier","doi":"10.1080/19491034.2020.1846836","DOIUrl":"10.1080/19491034.2020.1846836","url":null,"abstract":"<p><p>The functional organization of the plant nuclear envelope is gaining increasing attention through new connections made between nuclear envelope-associated proteins and important plant biological processes. Animal nuclear envelope proteins play roles in nuclear morphology, nuclear anchoring and movement, chromatin tethering and mechanical signaling. However, how these roles translate to functionality in a broader biological context is often not well understood. A surprising number of plant nuclear envelope-associated proteins are plant-unique, suggesting that separate functionalities evolved after the split of Opisthokonta and Streptophyta. Significant progress has now been made in discovering broader biological roles of plant nuclear envelope proteins, increasing the number of known plant nuclear envelope proteins, and connecting known proteins to chromatin organization, gene expression, and the regulation of nuclear calcium. The interaction of viruses with the plant nuclear envelope is another emerging theme. Here, we survey the recent developments in this still relatively new, yet rapidly advancing field.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":"11 1","pages":"330-346"},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19491034.2020.1846836","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38576813","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 Y Lee, C G Bisig, M N Conrad, Y Ditamo, L Previato de Almeida, M E Dresser, R J Pezza
{"title":"Telomere-led meiotic chromosome movements: recent update in structure and function.","authors":"C Y Lee, C G Bisig, M N Conrad, Y Ditamo, L Previato de Almeida, M E Dresser, R J Pezza","doi":"10.1080/19491034.2020.1769456","DOIUrl":"https://doi.org/10.1080/19491034.2020.1769456","url":null,"abstract":"<p><p>In S. cerevisiae prophase meiotic chromosomes move by forces generated in the cytoplasm and transduced to the telomere via a protein complex located in the nuclear membrane. We know that chromosome movements require actin cytoskeleton [13,31] and the proteins Ndj1, Mps3, and Csm4. Until recently, the identity of the protein connecting Ndj1-Mps3 with the cytoskeleton components was missing. It was also not known the identity of a cytoplasmic motor responsible for interacting with the actin cytoskeleton and a protein at the outer nuclear envelope. Our recent work [36] identified Mps2 as the protein connecting Ndj1-Mps3 with cytoskeleton components; Myo2 as the cytoplasmic motor that interacts with Mps2; and Cms4 as a regulator of Mps2 and Myo2 interaction and activities (Figure 1). Below we present a model for how Mps2, Csm4, and Myo2 promote chromosome movements by providing the primary connections joining telomeres to the actin cytoskeleton through the LINC complex.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":"11 9","pages":"111-116"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19491034.2020.1769456","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37938446","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":"Dynamics as a cause for the nanoscale organization of the genome.","authors":"Roman Barth, Genevieve Fourel, Haitham A Shaban","doi":"10.1080/19491034.2020.1763093","DOIUrl":"https://doi.org/10.1080/19491034.2020.1763093","url":null,"abstract":"<p><p>Chromatin 'blobs' were recently identified by live super-resolution imaging of labeled nucleosomes as pervasive but fleeting structural entities. However, the mechanisms leading to the formation of these blobs and their functional implications are unknown. We explore here whether causal relationships exist between parameters that characterize the chromatin blob dynamics and structure, by adapting a framework for spatio-temporal Granger-causality inference. Our analysis reveals that chromatin dynamics is a key determinant for both blob area and local density. Such causality, however, could be demonstrated only in 10-20% of the nucleus, suggesting that chromatin dynamics and structure at the nanometer scale are dominated by stochasticity. We show that the theory of active semiflexible polymers can be invoked to provide potential mechanisms leading to the organization of chromatin into blobs. Our results represent a first step toward elucidating the mechanisms that govern the dynamic and stochastic organization of chromatin in the cell nucleus.</p>","PeriodicalId":74323,"journal":{"name":"Nucleus (Austin, Tex.)","volume":"11 1","pages":"83-98"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/19491034.2020.1763093","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37972186","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}