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https://www.readbyqxmd.com/read/28525758/targeted-degradation-of-ctcf-decouples-local-insulation-of-chromosome-domains-from-genomic-compartmentalization
#1
Elphège P Nora, Anton Goloborodko, Anne-Laure Valton, Johan H Gibcus, Alec Uebersohn, Nezar Abdennur, Job Dekker, Leonid A Mirny, Benoit G Bruneau
The molecular mechanisms underlying folding of mammalian chromosomes remain poorly understood. The transcription factor CTCF is a candidate regulator of chromosomal structure. Using the auxin-inducible degron system in mouse embryonic stem cells, we show that CTCF is absolutely and dose-dependently required for looping between CTCF target sites and insulation of topologically associating domains (TADs). Restoring CTCF reinstates proper architecture on altered chromosomes, indicating a powerful instructive function for CTCF in chromatin folding...
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28525751/lamina-associated-domains-links-with-chromosome-architecture-heterochromatin-and-gene-repression
#2
REVIEW
Bas van Steensel, Andrew S Belmont
In metazoan cell nuclei, hundreds of large chromatin domains are in close contact with the nuclear lamina. Such lamina-associated domains (LADs) are thought to help organize chromosomes inside the nucleus and have been associated with gene repression. Here, we discuss the properties of LADs, the molecular mechanisms that determine their association with the nuclear lamina, their dynamic links with other nuclear compartments, and their proposed roles in gene regulation.
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28520954/h2b-ubiquitylation-and-the-histone-chaperone-asf1-cooperatively-mediate-the-formation-and-maintenance-of-heterochromatin-silencing
#3
Meng-Ying Wu, Chia-Yeh Lin, Hsin-Yi Tseng, Fei-Man Hsu, Pao-Yang Chen, Cheng-Fu Kao
Heterochromatin is a heritable form of gene repression, with critical roles in development and cell identity. Understanding how chromatin factors results in such repression is a fundamental question. Chromatin is assembled and disassembled during transcription, replication and repair by anti-silencing function 1 (Asf1), a highly conserved histone chaperone. Transcription and DNA replication are also affected by histone modifications that modify nucleosome dynamics, such as H2B ubiquitylation (H2Bub). We report here that H2Bub and Asf1 cooperatively promote transcriptional silencing at yeast telomeres and mating loci...
May 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28518126/techniques-to-induce-and-quantify-cellular-senescence
#4
Nicole Noren Hooten, Michele K Evans
In response to cellular stress or damage, proliferating cells can induce a specific program that initiates a state of long-term cell-cycle arrest, termed cellular senescence. Accumulation of senescent cells occurs with organismal aging and through continual culturing in vitro. Senescent cells influence many biological processes, including embryonic development, tissue repair and regeneration, tumor suppression, and aging. Hallmarks of senescent cells include, but are not limited to, increased senescence-associated β-galactosidase activity (SA-β-gal); p16(INK4A), p53, and p21 levels; higher levels of DNA damage, including γ-H2AX; the formation of Senescence-associated Heterochromatin Foci (SAHF); and the acquisition of a Senescence-associated Secretory Phenotype (SASP), a phenomenon characterized by the secretion of a number of pro-inflammatory cytokines and signaling molecules...
May 1, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28514774/demonstration-of-5-methylcytosine-rich-dna-sequences-in-chiroptera
#5
Michael Schmid, Claus Steinlein, Christian Lomb, Marianne Volleth
5-Methylcytosine-rich heterochromatic regions were demonstrated in metaphase chromosomes of 5 species of Chiroptera by indirect immunofluorescence using a monoclonal anti-5-methylcytosine antibody. These species belong to 4 genera and 2 families and are characterized by divergent karyotypes. One species (Glauconycteris beatrix) has an extremely low diploid chromosome number of 2n = 22 with only meta- to submetacentric elements and remarkably large amounts of constitutive heterochromatin located in the centromeric and pericentromeric regions of all chromosome pairs...
May 18, 2017: Cytogenetic and Genome Research
https://www.readbyqxmd.com/read/28500793/integrating-the-genomic-architecture-of-human-nucleolar-organizer-regions-with-the-biophysical-properties-of-nucleoli
#6
REVIEW
Hazel Mangan, Michael Ó Gailín, Brian McStay
Nucleoli are the sites of ribosome biogenesis and the largest membraneless sub-nuclear structures. They are intimately linked with growth and proliferation control and function as sensors of cellular stress. Nucleoli form around arrays of ribosomal gene (rDNA) repeats also called nucleolar organizer regions (NORs). In humans, NORs are located on the short arms of all five human acrocentric chromosomes. Multiple NORs contribute to the formation of large heterochromatin-surrounded nucleoli observed in most human cells...
May 13, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28500471/w-enriched-satellite-sequence-in-the-indian-meal-moth-plodia-interpunctella-lepidoptera-pyralidae
#7
Martina Dalíková, Magda Zrzavá, Svatava Kubíčková, František Marec
The W chromosome of most lepidopteran species represents the largest heterochromatin entity in the female genome. Although satellite DNA is a typical component of constitutive heterochromatin, there are only a few known satellite DNAs (satDNAs) located on the W chromosome in moths and butterflies. In this study, we isolated and characterized new satDNA (PiSAT1) from microdissected W chromosomes of the Indian meal moth, Plodia interpunctella. Even though the PiSAT1 is mainly localized near the female-specific segment of the W chromosome, short arrays of this satDNA also occur on autosomes and/or the Z chromosome...
May 12, 2017: Chromosome Research
https://www.readbyqxmd.com/read/28498365/inhibition-of-twist1-mediated-invasion-by-chk2-promotes-premature-senescence-in-p53-defective-cancer-cells
#8
Debasis Nayak, Anmol Kumar, Souneek Chakraborty, Reyaz Ur Rasool, Hina Amin, Archana Katoch, Veena Gopinath, Vidushi Mahajan, Mahesh K Zilla, Bilal Rah, Sumit G Gandhi, Asif Ali, Lekha Dinesh Kumar, Anindya Goswami
Twist1, a basic helix-loop-helix transcription factor is implicated as a key mediator of epithelial-mesenchymal transition (EMT) and metastatic dissemination in p53-deficient cancer cells. On the other hand, checkpoint kinase 2 (Chk2), a major cell cycle regulatory protein provides a barrier to tumorigenesis due to DNA damage response by preserving genomic stability of the cells. Here we demonstrate that Chk2 induction proficiently abrogates invasion, cell scattering and invadopodia formation ability of p53-mutated invasive cells by suppressing Twist1, indicating Chk2 confers vital role in metastasis prevention...
May 12, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28497540/meikin-associated-polo-like-kinase-specifies-bub1-distribution-in-meiosis-i
#9
Seira Miyazaki, Jihye Kim, Yuya Yamagishi, Tadashi Ishiguro, Yuki Okada, Yuji Tanno, Takeshi Sakuno, Yoshinori Watanabe
In meiosis I, sister chromatids are captured by microtubules emanating from the same pole (mono-orientation), and centromeric cohesion is protected throughout anaphase. Shugoshin, which is localized to centromeres depending on the phosphorylation of histone H2A by Bub1 kinase, plays a central role in protecting meiotic cohesin Rec8 from separase cleavage. Another key meiotic kinetochore factor, meikin, may regulate cohesion protection, although the underlying molecular mechanisms remain elusive. Here, we show that fission yeast Moa1 (meikin), which associates stably with CENP-C during meiosis I, recruits Plo1 (polo-like kinase) to the kinetochores and phosphorylates Spc7 (KNL1) to accumulate Bub1...
May 12, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28494440/nuclear-architecture-of-mouse-spermatocytes-chromosome-topology-heterochromatin-and-nucleolus
#10
Soledad Berrios
The nuclear organization of spermatocytes in meiotic prophase I is primarily determined by the synaptic organization of the bivalents that are bound by their telomeres to the nuclear envelope and described as arc-shaped trajectories through the 3D nuclear space. However, over this basic meiotic organization, a spermatocyte nuclear architecture arises that is based on higher-ordered patterns of spatial associations among chromosomal domains from different bivalents that are conditioned by the individual characteristics of chromosomes and the opportunity for interactions between their domains...
May 12, 2017: Cytogenetic and Genome Research
https://www.readbyqxmd.com/read/28489595/chromatin-remodeling-modulates-radiosensitivity-of-the-daughter-cells-derived-from-cell-population-exposed-to-low-and-high-let-irradiation
#11
Ping Wang, Dexiao Yuan, Fei Guo, Xiaoyan Chen, Lin Zhu, Hang Zhang, Chen Wang, Chunlin Shao
Radiation effects are dependent of linear energy transfer (LET), but it is still obscure whether the daughter cells (DCs) derived from irradiated population are radioresistance and much less the underlying mechanism. With the measurements of survival, proliferation and γH2AX foci, this study shows that the DCs from γ-ray irradiated cells (DCs-γ) became more radioresistant than its parent control without irradiation, but the radiosensitivity of DCs from α-particle irradiated cells (DCs-α) was not altered...
April 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28483815/drosophila-dalmatian-combines-sororin-and-shugoshin-roles-in-establishment-and-protection-of-cohesion
#12
Takashi Yamada, Eri Tahara, Mai Kanke, Keiko Kuwata, Tomoko Nishiyama
Sister chromatid cohesion is crucial to ensure chromosome bi-orientation and equal chromosome segregation. Cohesin removal via mitotic kinases and Wapl has to be prevented in pericentromeric regions in order to protect cohesion until metaphase, but the mechanisms of mitotic cohesion protection remain elusive in Drosophila Here, we show that dalmatian (Dmt), an ortholog of the vertebrate cohesin-associated protein sororin, is required for protection of mitotic cohesion in flies. Dmt is essential for cohesion establishment during interphase and is enriched on pericentromeric heterochromatin...
May 8, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28481278/combining-low-temperature-fluorescence-dna-hybridization-immunostaining-and-super-resolution-localization-microscopy-for-nano-structure-analysis-of-alu-elements-and-their-influence-on-chromatin-structure
#13
Matthias Krufczik, Aaron Sievers, Annkathrin Hausmann, Jin-Ho Lee, Georg Hildenbrand, Wladimir Schaufler, Michael Hausmann
Immunostaining and fluorescence in situ hybridization (FISH) are well established methods for specific labelling of chromatin in the cell nucleus. COMBO-FISH (combinatorial oligonucleotide fluorescence in situ hybridization) is a FISH method using computer designed oligonucleotide probes specifically co-localizing at given target sites. In combination with super resolution microscopy which achieves spatial resolution far beyond the Abbe Limit, it allows new insights into the nano-scaled structure and organization of the chromatin of the nucleus...
May 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28477128/analyzing-heterochromatic-dna-double-strand-break-dsb-repair-in-response-to-ionizing-radiation
#14
Karolin Klement, Aaron A Goodarzi
DNA damaging agents such as ionizing irradiation induce lesions in the DNA such as double strand breaks (DSBs). Depending on cell type, 10-25% of these DSBs are induced in heterochromatin. Heterochromatic DSBs are resolved with slow kinetics (compared to DSBs in euchromatin) and require ATM activity for repair. Investigating the underlying causes of the slow component of DSB repair and the role of individual response factors in this process provides insight into DSB response pathways and will further the understanding of diseases where such pathways are dysfunctional due to mutation...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28476938/chromatin-organization-at-the-nuclear-periphery-as-revealed-by-image-analysis-of-structured-illumination-microscopy-data
#15
Jindřiška Fišerová, Michaela Efenberková, Tomáš Sieger, Miloslava Maninová, Jana Uhlířová, Pavel Hozák
Nuclear periphery (NP) plays substantial role in chromatin organization. Heterochromatin at the NP is intermitted with active chromatin surrounding nuclear pore complexes (NPCs), however, details of the peripheral chromatin organization are missing. To discern the distributions of epigenetic marks at the NP of HeLa nuclei, we used structured illumination microscopy combined with a new MATLAB software tool for an automatic NP and NPC detection, measurements of fluorescent intensity and statistical analysis of measured data...
May 5, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28476860/an-evolutionary-perspective-on-yeast-mating-type-switching
#16
REVIEW
Sara J Hanson, Kenneth H Wolfe
Cell differentiation in yeast species is controlled by a reversible, programmed DNA-rearrangement process called mating-type switching. Switching is achieved by two functionally similar but structurally distinct processes in the budding yeast Saccharomyces cerevisiae and the fission yeast Schizosaccharomyces pombe In both species, haploid cells possess one active and two silent copies of the mating-type locus (a three-cassette structure), the active locus is cleaved, and synthesis-dependent strand annealing is used to replace it with a copy of a silent locus encoding the opposite mating-type information...
May 2017: Genetics
https://www.readbyqxmd.com/read/28466841/arabidopsis-proteins-with-a-transposon-related-domain-act-in-gene-silencing
#17
Yoko Ikeda, Thierry Pélissier, Pierre Bourguet, Claude Becker, Marie-Noëlle Pouch-Pélissier, Romain Pogorelcnik, Magdalena Weingartner, Detlef Weigel, Jean-Marc Deragon, Olivier Mathieu
Transposable elements (TEs) are prevalent in most eukaryotes, and host genomes have devised silencing strategies to rein in TE activity. One of these, transcriptional silencing, is generally associated with DNA methylation and short interfering RNAs. Here we show that the Arabidopsis genes MAIL1 and MAIN define an alternative silencing pathway independent of DNA methylation and short interfering RNAs. Mutants for MAIL1 or MAIN exhibit release of silencing and appear to show impaired condensation of pericentromeric heterochromatin...
May 3, 2017: Nature Communications
https://www.readbyqxmd.com/read/28461078/isolation-and-identification-of-senescent-renal-tubular-epithelial-cells-using-immunomagnetic-beads-based-on-dcr2
#18
Jia Chen, Ke-Hong Chen, Bi-Qiong Fu, Weiwei Zhang, Huanzi Dai, Li-Rong Lin, Li-Ming Wang, Ya-Ni He
Cell senescence plays a major role in the progression of tumors and chronic conditions such as diabetes and chronic kidney disease. Senescent cells are an important model for the study of aging-related diseases, and there is currently no efficient method for sorting out senescent cells. Decoy receptor 2 (DcR2) is a transmembrane receptor of the tumor necrosis factor superfamily, which is specifically expressed in senescent cells. In this study, we used magnetic activated cell sorting (MACS) isolation of a highly-pure populations DcR2-positive renal tubular epithelial cells (RTECs) based on three senescent cell models including the fifth passage cells, advanced glycation end-products (AGEs)- and H2O2-induced cells...
April 28, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28459455/dna-sequence-homology-induces-cytosine-to-thymine-mutation-by-a-heterochromatin-related-pathway-in-neurospora
#19
Eugene Gladyshev, Nancy Kleckner
Most eukaryotic genomes contain substantial amounts of repetitive DNA organized in the form of constitutive heterochromatin and associated with repressive epigenetic modifications, such as H3K9me3 and C5 cytosine methylation (5mC). In the fungus Neurospora crassa, H3K9me3 and 5mC are catalyzed, respectively, by a conserved SUV39 histone methyltransferase, DIM-5, and a DNMT1-like cytosine methyltransferase, DIM-2. Here we show that DIM-2 can also mediate repeat-induced point mutation (RIP) of repetitive DNA in N...
May 1, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28459194/metabolic-perturbation-of-epigenome-by-inhibiting-s-adenosylhomocysteine-hydrolase-elicits-senescence-through-dna-damage-response-in-hepatoma-cells
#20
Guozhen Wu, Ning Wang, Ying Luo, Yanyan Zhang, Peng Wang, Zhengyan Zhu, Yingtang Gao, Zhi Du, Bin Yang
Cellular senescence is a key physiological barrier against tumor and represents an option for therapeutic intervention. One pivotal intracellular stimulus causing senescence is DNA damage response, while the senescence-associated heterochromatin in cancer limits the strength of the DNA damage response to endogenous genotoxic stress or DNA-damaging agents. Therefore, targeting the maintenance of compacted chromatin in cancer cells represents an optional intervention to improve the therapeutic efficacy in cancer treatment...
May 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
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