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Nucleus

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https://www.readbyqxmd.com/read/28430006/evolutionary-changes-in-lamin-expression-in-the-vertebrate-lineage
#1
Reimer Stick, Annette Peter
The nuclear lamina is involved in fundamental nuclear functions and provides mechanical stability to the nucleus. Lamin filaments form a meshwork closely apposed to the inner nuclear membrane and a small fraction of lamins exist in the nuclear interior. Mutations in lamin genes cause severe hereditary diseases, the laminopathies. During vertebrate evolution the lamin protein family has expanded. While most vertebrate genomes contain four lamin genes, encoding the lamins A, B1, B2, and LIII, the majority of non-vertebrate genomes harbor only a single lamin gene...
April 21, 2017: Nucleus
https://www.readbyqxmd.com/read/28406743/the-readers-of-unacetylated-p53-represent-a-new-class-of-acidic-domain-proteins
#2
Donglai Wang, Ning Kon, Omid Tavana, Wei Gu
Acetylation of non-histone proteins plays important roles in regulating protein functions but the mechanisms of action are poorly understood. Our recent study uncovered a previously unknown mechanism by which C-terminal domain (CTD) acetylation of p53 serves as a "switch" to determine the interaction between a unique group of acidic domain-containing proteins and p53, as well as revealed that acidic domains may act as a novel class of "readers" for unacetylated p53. However, the properties of acidic domain "readers" are not well elucidated yet...
April 13, 2017: Nucleus
https://www.readbyqxmd.com/read/28406741/bridging-the-dynamics-and-organization-of-chromatin-domains-by-mathematical-modeling
#3
Soya Shinkai, Tadasu Nozaki, Kazuhiro Maeshima, Yuichi Togashi
The genome is three-dimensionally organized in the cell, and the mammalian genome DNA is partitioned into submegabase-sized chromatin domains. Genome functions are regulated within and across the domains according to their organization, whereas the chromatin itself is highly dynamic. However, the details of such dynamic organization of chromatin domains in living cells remain unclear. To unify chromatin dynamics and organization, we recently demonstrated that structural information of chromatin domains in living human cells can be extracted from analyses of the subdiffusive nucleosome movement using mathematical modeling...
April 13, 2017: Nucleus
https://www.readbyqxmd.com/read/28406740/alpha-satellite-dna-variation-and-function-of-the-human-centromere
#4
Lori L Sullivan, Kimberline Chew, Beth A Sullivan
Genomic variation is a source of functional diversity that is typically studied in genic and non-coding regulatory regions. However, the extent of variation within noncoding portions of the human genome, particularly highly repetitive regions, and the functional consequences are not well understood. Satellite DNA, including alpha satellite DNA found at human centromeres, comprises up to 10% of the genome, but is difficult to study because its repetitive nature hinders contiguous sequence assemblies. We recently described variation within alpha satellite DNA that affects centromere function...
April 13, 2017: Nucleus
https://www.readbyqxmd.com/read/28402725/visualization-of-pml-nuclear-import-complexes-reveals-fg-repeat-nucleoporins-at-cargo-retrieval-sites
#5
Anna Lång, Jens Eriksson, Kay Oliver Schink, Emma Lång, Pernille Blicher, Anna Połeć, Andreas Brech, Bjørn Dalhus, Stig Ove Bøe
Selective nuclear import in eukaryotic cells involves sequential interactions between nuclear import receptors and phenylalanine-glycine (FG)-repeat nucleoporins. Traditionally, binding of cargoes to import receptors is perceived as a nuclear pore complex independent event, while interactions between import complexes and nucleoporins are thought to take place at the nuclear pores. However, studies have shown that nucleoporins are mobile and not static within the nuclear pores, suggesting that they may become engaged in nuclear import prior to nuclear pore entry...
April 12, 2017: Nucleus
https://www.readbyqxmd.com/read/28287898/consequences-of-a-tight-squeeze-nuclear-envelope-rupture-and-repair
#6
Philipp Isermann, Jan Lammerding
Cell migration through tight spaces can induce substantial deformations of the nucleus and cause nuclear envelope (NE) rupture, resulting in uncontrolled exchange of nuclear and cytosolic proteins. These events can cause DNA damage and, in severe cases, nuclear fragmentation, challenging the integrity of the genomic material. Cells overcome NE ruptures during interphase by repairing the NE using components of the endosomal sorting complexes required for transport (ESCRT) machinery. Paralleling the molecular mechanism employed during NE reformation in late mitosis, ESCRT-III subunits and the associated AAA-ATPase VPS4B are recruited to NE rupture sites and help restore NE integrity...
March 13, 2017: Nucleus
https://www.readbyqxmd.com/read/28340334/advances-in-phase-plate-cryo-em-imaging-of-dna-and-nucleosomes
#7
Eugene Y D Chua, Sara Sandin
Contrast in electron cryo-microscopy (cryo-EM) is limited by the weak phase and radiation sensitive nature of biologic samples embedded in vitrified ice. We have recently shown that a new contrast enhancement technique utilizing the Volta phase plate can be combined with single particle analysis to determine the structure of a small chromatin complex, the nucleosome core particle, at near-atomic resolution. Here, we discuss advantages and limitations of the technique in terms of data collection, particle detection, and visualization of individual DNA molecules and higher-order chromatin structure...
February 7, 2017: Nucleus
https://www.readbyqxmd.com/read/28152338/dynamic-regulation-of-nuclear-architecture-and-mechanics-a-rheostatic-role-for-the-nucleus-in-tailoring-cellular-mechanosensitivity
#8
Stephen D Thorpe, David A Lee
Nuclear architecture, a function of both chromatin and nucleoskeleton structure, is known to change with stem cell differentiation and differs between various somatic cell types. These changes in nuclear architecture are associated with the regulation of gene expression and genome function in a cell-type specific manner. Biophysical stimuli are known effectors of differentiation and also elicit stimuli-specific changes in nuclear architecture. This occurs via the process of mechanotransduction whereby extracellular mechanical forces activate several well characterized signaling cascades of cytoplasmic origin, and potentially some recently elucidated signaling cascades originating in the nucleus...
February 2, 2017: Nucleus
https://www.readbyqxmd.com/read/28146370/identification-of-candidates-for-interacting-partners-of-the-tail-domain-of-dcnmcp1-a-major-component-of-the-daucus-carota-nuclear-lamina-like-structure
#9
Ryota Mochizuki, Daisuke Tsugama, Michihiro Yamazaki, Kaien Fujino, Kiyoshi Masuda
NMCP/CRWN (NUCLEAR MATRIX CONSTITUENT PROTEIN/CROWDED NUCLEI) is a major component of a protein fibrous meshwork (lamina-like structure) on the plant inner nuclear membrane. NMCP/CRWN contributes to regulating nuclear shape and nuclear functions. An NMCP/CRWN protein in Daucus carota (DcNMCP1) is localized to the nuclear periphery in interphase cells, and surrounds chromosomes in cells in metaphase and anaphase. The N-terminal region and the C-terminal region of DcNMCP1 are both necessary for localizing DcNMCP1 to the nuclear periphery...
February 1, 2017: Nucleus
https://www.readbyqxmd.com/read/28129029/chromosome-conformation-and-gene-expression-patterns-differ-profoundly-in-human-fibroblasts-grown-in-spheroids-versus-monolayers
#10
Haiming Chen, Laura Seaman, Sijia Liu, Thomas Ried, Indika Rajapakse
Human cells derived for in vitro cultures are conventionally grown as adherent monolayers (2 D) which do not resemble natural three dimensional (3 D) tissue architecture. We examined genome structure with chromosome conformation capture (Hi-C) and gene expression with RNA-seq in fibroblasts derived from human foreskin grown in 2 D and 3 D conditions. Our combined analysis of Hi-C and RNA-seq data shows a large number of differentially expressed genes between 2 D and 3 D cells, and these changes are localized in genomic regions that displayed structural changes...
January 27, 2017: Nucleus
https://www.readbyqxmd.com/read/28406751/repetitive-dna-loci-and-their-modulation-by-the-non-canonical-nucleic-acid-structures-r-loops-and-g-quadruplexes
#11
Amanda C Hall, Lauren A Ostrowski, Violena Pietrobon, Karim Mekhail
Cells have evolved intricate mechanisms to maintain genome stability despite allowing mutational changes to drive evolutionary adaptation. Repetitive DNA sequences, which represent the bulk of most genomes, are a major threat to genome stability often driving chromosome rearrangements and disease. The major source of repetitive DNA sequences and thus the most vulnerable constituents of the genome are the rDNA (rDNA) repeats, telomeres, and transposable elements. Maintaining the stability of these loci is critical to overall cellular fitness and lifespan...
March 4, 2017: Nucleus
https://www.readbyqxmd.com/read/28406750/sirtuins-and-dna-damage-repair-sirt7-comes-to-play
#12
Berta N Vazquez, Joshua K Thackray, Lourdes Serrano
Aging is characterized by a cumulative loss of genome integrity, which involves chromatin reorganization, transcriptional dysregulation and the accumulation of DNA damage. Sirtuins participate in the protection against these aging processes by promoting genome homeostasis in response to cellular stress. We recently reported that SirT7(-/-) mice suffer from partial embryonic lethality and a progeroid like phenotype. At the cellular level, SIRT7 depletion results in the impaired repair of DNA double-strand breaks (DSBs), one the most dangerous DNA lesions, leading to genome instability...
March 4, 2017: Nucleus
https://www.readbyqxmd.com/read/28406749/nucleosome-repositioning-during-differentiation-of-a-human-myeloid-leukemia-cell-line
#13
Vladimir B Teif, Jan-Philipp Mallm, Tanvi Sharma, David B Mark Welch, Karsten Rippe, Roland Eils, Jörg Langowski, Ada L Olins, Donald E Olins
Cell differentiation is associated with changes in chromatin organization and gene expression. In this study, we examine chromatin structure following differentiation of the human myeloid leukemia cell line (HL-60/S4) into granulocytes with retinoic acid (RA) or into macrophage with phorbol ester (TPA). We performed ChIP-seq of histone H3 and its modifications, analyzing changes in nucleosome occupancy, nucleosome repeat length, eu-/heterochromatin redistribution and properties of epichromatin (surface chromatin adjacent to the nuclear envelope)...
March 4, 2017: Nucleus
https://www.readbyqxmd.com/read/28152343/transcriptomes-reflect-the-phenotypes-of-undifferentiated-granulocyte-and-macrophage-forms-of-hl-60-s4-cells
#14
David B Mark Welch, Anna Jauch, Jörg Langowski, Ada L Olins, Donald E Olins
To understand the chromatin changes underlying differential gene expression during induced differentiation of human leukemic HL-60/S4 cells, we conducted RNA-Seq analysis on quadruplicate cultures of undifferentiated, granulocytic- and macrophage-differentiated cell forms. More than half of mapped genes exhibited altered transcript levels in the differentiated cell forms. In general, more genes showed increased mRNA levels in the granulocytic form and in the macrophage form, than showed decreased levels. The majority of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were significantly enriched in genes that exhibited differential transcript levels after either RA or TPA treatment...
March 4, 2017: Nucleus
https://www.readbyqxmd.com/read/28112995/nuclear-membrane-stretch-and-its-role-in-mechanotransduction
#15
Balázs Enyedi, Philipp Niethammer
Most research in nuclear mechanotransduction has focused on the nuclear lamina and lamin binding proteins. These structures provide mechanical stability to the nucleus, establish a link between the cytoskeleton and chromatin, and can transmit mechanical signals. At the same time, mechanical perturbations to the nucleus also affect its phospholipid membranes. In this commentary, we discuss how changes in nuclear membrane tension can mediate mechanotransduction.
March 4, 2017: Nucleus
https://www.readbyqxmd.com/read/28085555/sox9-chromatin-folding-domains-correlate-with-its-real-and-putative-distant-cis-regulatory-elements
#16
Marta Smyk, Kadir Caner Akdemir, Paweł Stankiewicz
Evolutionary conserved transcription factor SOX9, encoded by the dosage sensitive SOX9 gene on chromosome 17q24.3, plays an important role in development of multiple organs, including bones and testes. Heterozygous point mutations and genomic copy-number variant (CNV) deletions involving SOX9 have been reported in patients with campomelic dysplasia (CD), a skeletal malformation syndrome often associated with male-to-female sex reversal. Balanced and unbalanced structural genomic variants with breakpoints mapping up to 1...
March 4, 2017: Nucleus
https://www.readbyqxmd.com/read/28072566/guard-the-guardian-a-crl4-ligase-stands-watch-over-histone-production
#17
Fabienne Lampert, Mia M L Brodersen, Matthias Peter
Histones are evolutionarily conserved proteins that together with DNA constitute eukaryotic chromatin in a defined stoichiometry. Core histones are dynamic scaffolding proteins that undergo a myriad of post-translational modifications, which selectively engage chromosome condensation, replication, transcription and DNA damage repair. Cullin4-RING ubiquitin E3 ligases are known to hold pivotal roles in a wide spectrum of chromatin biology ranging from chromatin remodeling and transcriptional repression, to sensing of cytotoxic DNA lesions...
March 4, 2017: Nucleus
https://www.readbyqxmd.com/read/28068183/nucleolar-aggresomes-mediate-release-of-pericentric-heterochromatin-and-nuclear-destruction-of-genotoxically-treated-cancer-cells
#18
Kristine Salmina, Anda Huna, Inna Inashkina, Alexander Belyayev, Jekabs Krigerts, Ladislava Pastova, Alejandro Vazquez-Martin, Jekaterina Erenpreisa
The role of the nucleolus and autophagy in maintenance of nuclear integrity is poorly understood. In addition, the mechanisms of nuclear destruction in cancer cells senesced after conventional chemotherapy are unclear. In an attempt to elucidate these issues, we studied teratocarcinoma PA1 cells treated with Etoposide (ETO), focusing on the nucleolus. Following treatment, most cells enter G2 arrest, display persistent DNA damage and activate p53, senescence, and macroautophagy markers. 2-5 µm sized nucleolar aggresomes (NoA) containing fibrillarin (FIB) and damaged rDNA, colocalized with ubiquitin, pAMPK, and LC3-II emerge, accompanied by heterochromatin fragments, when translocated perinuclearly...
March 4, 2017: Nucleus
https://www.readbyqxmd.com/read/28060558/the-connection-between-brg1-ctcf-and-topoisomerases-at-tad-boundaries
#19
A Rasim Barutcu, Jane B Lian, Janet L Stein, Gary S Stein, Anthony N Imbalzano
The eukaryotic genome is partitioned into topologically associating domains (TADs). Despite recent advances characterizing TADs and TAD boundaries, the organization of these structures is an important dimension of genome architecture and function that is not well understood. Recently, we demonstrated that knockdown of BRG1, an ATPase driving the chromatin remodeling activity of mammalian SWI/SNF enzymes, globally alters long-range genomic interactions and results in a reduction of TAD boundary strength. We provided evidence suggesting that this effect may be due to BRG1 affecting nucleosome occupancy around CTCF sites present at TAD boundaries...
March 4, 2017: Nucleus
https://www.readbyqxmd.com/read/28060557/control-of-nuclear-organization-by-f-actin-binding-proteins
#20
Karin Pfisterer, Asier Jayo, Maddy Parsons
The regulation of nuclear shape and deformability is a key factor in controlling diverse events from embryonic development to cancer cell metastasis, but the mechanisms governing this process are still unclear. Our recent study demonstrated an unexpected role for the F-actin bundling protein fascin in controlling nuclear plasticity through a direct interaction with Nesprin-2. Nesprin-2 is a component of the LINC complex that is known to couple the F-actin cytoskeleton to the nuclear envelope. We demonstrated that fascin, which is predominantly associated with peripheral F-actin rich filopodia, binds directly to Nesprin-2 at the nuclear envelope in a range of cell types...
March 4, 2017: Nucleus
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