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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
Travis J Gould, Katalin Tóth, Norbert Mücke, Jörg Langowski, Alexandra S Hakusui, Ada L Olins, Donald E Olins
Epichromatin is identified by immunostaining fixed and permeabilized cells with particular bivalent anti-nucleosome antibodies (mAbs PL2-6 and 1H6). During interphase, epichromatin resides adjacent to the inner nuclear membrane; during mitosis, at the outer surface of mitotic chromosomes. By STED (stimulated emission depletion) microscopy, PL2-6 stained interphase epichromatin is ∼76 nm thick and quite uniform; mitotic epichromatin is more variable in thickness, exhibiting a "wrinkled" surface with an average thickness of ∼78 nm...
September 29, 2017: Nucleus
Juliana S Capitanio, Ben Montpetit, Richard W Wozniak
The nucleoporin Nup98 has been linked to the regulation of transcription and RNA metabolism, (1-3) but the mechanisms by which Nup98 contributes to these processes remains largely undefined. Recently, we uncovered interactions between Nup98 and several DExH/D-box proteins (DBPs), a protein family well-known for modulating gene expression and RNA metabolism. (4-6) Analysis of Nup98 and one of these DBPs, DHX9, showed that they directly interact, their association is facilitated by RNA, and Nup98 binding stimulates DHX9 ATPase activity...
September 21, 2017: Nucleus
Olga Shubernetskaya, Dmitry Skvortsov, Sergey Evfratov, Maria Rubtsova, Elena Belova, Olga Strelkova, Varvara Cherepaninets, Oxana Zhironkina, Alexey Olovnikov, Maria Zvereva, Olga Dontsova, Igor Kireev
During a cell's lifespan, DNA break formation is a common event, associated with many processes, from replication to apoptosis. Most of DNA breaks are readily repaired, but some are meant to persist in time, such as the chromosome ends, protected by telomeres. Besides them, eukaryotic genomes comprise shorter stretches of interstitial telomeric repeats. We assumed that the latter may also be associated with the formation of DNA breaks meant to persist in time. In zebrafish and mouse embryos, cells containing numerous breakage foci were identified...
September 15, 2017: Nucleus
Fouziya R Shah, Younus A Bhat, Ajazul H Wani
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...
September 14, 2017: Nucleus
Debaditya De, Satish Kallappagoudar, Jae-Min Lim, Rashmi U Pathak, Rakesh K Mishra
Boundary Element-Associated Factor 32 (BEAF 32) is a sequence specific DNA binding protein involved in functioning of chromatin domain boundaries in Drosophila. Several studies also show it to be involved in transcriptional regulation of a large number of genes, many of which are annotated to have cell cycle, development and differentiation related function. Since post-translational modifications (PTMs) of proteins add to their functional capacity, we investigated the PTMs on BEAF 32. The protein is known to be phosphorylated and O-GlcNAcylated...
September 14, 2017: Nucleus
Eshagh Dorafshan, Tatyana G Kahn, Yuri B Schwartz
Polycomb Group (PcG) proteins epigenetically repress key developmental genes and thereby control alternative cell fates. PcG proteins act as complexes that can modify histones and these histone modifications play a role in transmitting the "memory" of the repressed state as cells divide. Here we consider mainstream models that link histone modifications to hierarchical recruitment of PcG complexes and compare them to results of a direct test of interdependence between PcG complexes for recruitment to Drosophila genes...
September 14, 2017: Nucleus
Benjamin Alleva, Sarit Smolikove
Meiosis is a specialized cellular division occurring in organisms capable of sexual reproduction that leads to the formation of gametes containing half of the original chromosome number. During the earliest stage of meiosis, prophase I, pairing of homologous chromosomes is achieved in preparation for their proper distribution in the coming divisions. An important question is how do homologous chromosomes find each other and establish pairing interactions. Early studies demonstrated that chromosomes are dynamic in nature and move during this early stage of meiosis...
September 11, 2017: Nucleus
Emily DeBoy, Madaiah Puttaraju, Parthav Jailwala, Manjula Kasoji, Maggie Cam, Tom Misteli
The nuclear lamina is a proteinaceous meshwork situated underneath the inner nuclear membrane and is composed of nuclear lamin proteins, which are type-V intermediate filaments. The LMNA gene gives rise to lamin A and lamin C through alternative splicing. Mutations in LMNA cause multiple diseases known as laminopathies, including Hutchinson-Gilford Progeria Syndrome (HGPS), a premature aging disorder caused by a point mutation that activates a cryptic 5' splice site in exon 11, resulting in a 150 bp deletion in the LMNA mRNA and the production of the dominant lamin A isoform progerin...
August 31, 2017: Nucleus
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