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M Soheilypour, M Mofrad
Despite extensive research on how mRNAs are quality controlled prior to export into the cytoplasm, the exact underlying mechanisms are still under debate. Specifically, it is unclear how quality control proteins at the entry of the nuclear pore complex (NPC) distinguish normal and aberrant mRNAs. While some of the involved components are suggested to act as switches and recruit different factors to normal versus aberrant mRNAs, some experimental and computational evidence suggests that the combined effect of the regulated stochastic interactions between the involved components could potentially achieve an efficient quality control of mRNAs...
February 12, 2018: Nucleus
David Lando, Tim J Stevens, Srinjan Basu, Ernest D Laue
Single-cell chromosome conformation capture approaches are revealing the extent of cell-to-cell variability in the organization and packaging of genomes. These single-cell methods, unlike their multi-cell counterparts, allow straightforward computation of realistic chromosome conformations that may be compared and combined with other, independent, techniques to study 3D structure. Here we discuss how single-cell Hi-C and subsequent 3D genome structure determination allows comparison with data from microscopy...
February 12, 2018: Nucleus
Jekaterina Erenpreisa, Jekabs Krigerts, Kristine Salmina, Turs Selga, Hermanis Sorokins, Talivaldis Freivalds
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...
January 24, 2018: Nucleus
C A Brackley, J Johnson, D Michieletto, A N Morozov, M Nicodemi, P R Cook, D Marenduzzo
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...
January 4, 2018: Nucleus
Aleksander Szczurek, Udo Birk, Hans Knecht, Jurek Dobrucki, Sabine Mai, Christoph Cremer
Methods of super-resolving light microscopy (SRM) have found an exponentially growing range of applications in cell biology, including nuclear structure analyses. Recent developments have proven that Single Molecule Localization Microscopy (SMLM), a type of SRM, is particularly useful for enhanced spatial analysis of the cell nucleus due to its highest resolving capability combined with very specific fluorescent labeling. In this commentary we offer a brief review of the latest methodological development in the field of SMLM of chromatin designated DNA Structure Fluctuation Assisted Binding Activated Localization Microscopy (abbreviated as fBALM) as well as its potential future applications in biology and medicine...
January 3, 2018: Nucleus
Lukasz Majewski, Jolanta Nowak, Magdalena Sobczak, Olena Karatsai, Serhiy Havrylov, Robert Lenartowski, Malgorzata Suszek, Marta Lenartowska, Maria Jolanta Redowicz
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...
January 2, 2018: Nucleus
Evgeny Smirnov, Matúš Hornáček, Tomáš Vacík, Dušan Cmarko, Ivan Raška
The large number of works based on new single-cell and single-gene techniques show that individual genes can be transcribed in short bursts or pulses accompanied by changes in pulsing frequencies. Since so many examples of such discontinuous or fluctuating transcription have been found from prokaryotes to mammals, it now seems to be a common mode of gene expression. In this review we discuss the occurrence of the transcriptional fluctuations, the techniques used for their detection, their putative causes, kinetic characteristics, and probable physiological significance...
December 29, 2017: Nucleus
Emmanuelle Fabre, Christophe Zimmer
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...
December 22, 2017: Nucleus
Andrew D Stephens, Edward J Banigan, John F Marko
The cell nucleus houses, protects, and arranges the genome within the cell. Therefore, nuclear mechanics and morphology are important for dictating gene regulation, and these properties are perturbed in many human diseases, such as cancers and progerias. The field of nuclear mechanics has long been dominated by studies of the nuclear lamina, the intermediate filament shell residing just beneath the nuclear membrane. However, a growing body of work shows that chromatin and chromatin-related factors within the nucleus are an essential part of the mechanical response of the cell nucleus to forces...
December 11, 2017: Nucleus
Roman Petrovsky, Jörg Großhans
The nuclear lamina is involved in numerous cellular functions, such as gene expression, nuclear organization, nuclear stability, and cell proliferation. The mechanism underlying the involvement of lamina is often not clear, especially in physiological or developmental contexts. Here we investigate the role and activity of farnesylated lamina proteins Lamin (Lam) and Kugelkern (Kuk) in proliferation control of intestinal stem cells (ISCs) in adult Drosophila flies. We found that ISCs mutant for Lam or kuk proliferate, whereas overexpression of Lam or Kuk strongly suppressed proliferation...
December 6, 2017: Nucleus
Clare Rogerson, Daniele Bergamaschi, Ryan Flo'shaughnessy
Eukaryotic nuclei are essential organelles, storing the majority of the cellular DNA, comprising the site of most DNA and RNA synthesis, controlling gene expression and therefore regulating cellular function. The majority of mammalian cells retain their nucleus throughout their lifetime, however, in three mammalian tissues the nucleus is entirely removed and its removal is essential for cell function. Lens fibre cells, erythroblasts and epidermal keratinocytes all lose their nucleus in the terminal differentiation pathways of these cell types...
December 5, 2017: Nucleus
Jian Chen, EnLi, Jinsheng Lai
Nucleosomes are the fundamental units of eukaryotic chromatin and can modulate the DNA accessibility for transcriptional regulatory elements. Many studies have demonstrated the effect of nucleosome organization on gene transcription level and transcriptional plasticity upon different conditions. Our recent study showed that nucleosome organization also plays an important role in modulating the plasticity of gene transcriptional status in maize. Here, we integrated our findings with previous studies on the role of nucleosome organization in regulation of gene transcription...
December 5, 2017: Nucleus
Su-Jin Heo, Brian D Cosgrove, Eric N Dai, Robert L Mauck
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...
November 3, 2017: Nucleus
A Zachary Ostrow, Oscar M Aparicio
Forkhead Box (Fox) DNA binding proteins control multiple genome activities, including transcription, replication, and repair. These activities are organized spatially and temporally in the nucleus, and Fox proteins Fkh1 and Fkh2 have emerged as regulators of long-range chromosomal interactions involved with these activities, such as the clustering of replication origins programmed for early initiation. Fkh1 and Fkh2 bind a subset of replication origins and are thought to dimerize to mediate long-range chromosomal contacts between these origins...
November 3, 2017: Nucleus
Aude Guénolé, Gaëlle Legube
Translocations are dramatic genomic rearrangements due to aberrant rejoining of distant DNA ends that can trigger cancer onset and progression. Translocations frequently occur in genes, yet the mechanisms underlying their formation remain poorly understood. One potential mechanism involves DNA Double Strand Break mobility and juxtaposition (i.e. clustering), an event that has been intensively debated over the past decade. Using Capture Hi-C, we recently found that DSBs do in fact cluster in human nuclei but only when induced in transcriptionally active genes...
November 3, 2017: Nucleus
Atsuhiko Fukuto, Masae Ikura, Tsuyoshi Ikura, Jiying Sun, Yasunori Horikoshi, Hiroki Shima, Kazuhiko Igarashi, Masayuki Kusakabe, Masahiko Harata, Naoki Horikoshi, Hitoshi Kurumizaka, Yoshiaki Kiuchi, Satoshi Tashiro
Histone exchange and histone post-translational modifications play important roles in the regulation of DNA metabolism, by re-organizing the chromatin configuration. We previously demonstrated that the histone variant H2A.Z-2 is rapidly exchanged at damaged sites after DNA double strand break induction in human cells. In yeast, the small ubiquitin-like modifier (SUMO) modification of H2A.Z is involved in the DNA damage response. However, whether the SUMO modification regulates the exchange of human H2A.Z-2 at DNA damage sites remains unclear...
November 2, 2017: Nucleus
Maximiliano A D'Angelo
Nuclear pore complexes (NPCs), the channels connecting the nucleus with the cytoplasm, are the largest protein structures of the nuclear envelope. In addition to their role in regulating nucleocytoplasmic transport, increasing evidence shows that these multiprotein structures play central roles in the regulation of gene activity. In light of recent discoveries, NPCs are emerging as scaffolds that mediate the regulation of specific gene sets at the nuclear periphery. The function of NPCs as genome organizers and hubs for transcriptional regulation provides additional evidence that the compartmentalization of genes and transcriptional regulators within the nuclear space is an important mechanism of gene expression regulation...
November 2, 2017: Nucleus
Zdravko J Lorković, Frédéric Berger
Repair of damaged DNA requires the activation of kinases, which in turn phosphorylate diverse proteins including histone H2A.X, an event conserved from yeast to human. By combining genetics, biochemical, and cytological approaches, we recently reported that, in addition to H2A.X, phosphorylation of histone variant H2A.W.7 is required for DNA damage response in Arabidopsis. This work provides direct evidence for the functional diversification of plant-specific H2A.W histone variants, which are tightly associated with heterochromatin...
October 30, 2017: Nucleus
Anders S Hansen, Claudia Cattoglio, Xavier Darzacq, Robert Tjian
Mammalian genomes are folded into spatial domains, which regulate gene expression by modulating enhancer-promoter contacts. Here, we review recent studies on the structure and function of Topologically Associating Domains (TADs) and chromatin loops. We discuss how loop extrusion models can explain TAD formation and evidence that TADs are formed by the ring-shaped protein complex, cohesin, and that TAD boundaries are established by the DNA-binding protein, CTCF. We discuss our recent genomic, biochemical and single-molecule imaging studies on CTCF and cohesin, which suggest that TADs and chromatin loops are dynamic structures...
October 27, 2017: Nucleus
Victor V Lobanenkov, Gabriel E Zentner
CCCTC-binding factor (CTCF) is a conserved, essential regulator of chromatin architecture containing a unique array of 11 zinc fingers (ZFs). Gene duplication and sequence divergence during early amniote evolution generated the CTCF paralog Brother Of the Regulator of Imprinted Sites (BORIS), which has a DNA binding specificity identical to that of CTCF but divergent N- and C-termini. While healthy somatic tissues express only CTCF, CTCF and BORIS are normally co-expressed in meiotic and post-meiotic germ cells, and aberrant activation of BORIS occurs in tumors and some cancer cell lines...
October 27, 2017: Nucleus
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