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https://www.readbyqxmd.com/read/28528697/an-embryonic-stem-cell-specific-nurd-complex-functions-through-interaction-with-wdr5
#1
Ly-Sha Ee, Kurtis N McCannell, Yang Tang, Nancy Fernandes, W Rod Hardy, Michael R Green, Feixia Chu, Thomas G Fazzio
The Nucleosome Remodeling and Deacetylase (NuRD) complex is a chromatin regulatory complex that functions as a transcriptional co-repressor in metazoans. The NuRD subunit MBD3 is essential for targeting and assembly of a functional NuRD complex as well as embryonic stem cell (ESC) pluripotency. Three MBD3 isoforms (MBD3A, MBD3B, and MBD3C) are expressed in mouse. Here, we find that the MBD3C isoform contains a unique 50-amino-acid N-terminal region that is necessary for MBD3C to specifically interact with the histone H3 binding protein WDR5...
May 17, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28526651/disruption-of-nnat-nap1l5-and-mkrn3-dna-methylation-and-transcription-in-rabbit-parthenogenetic-fetuses
#2
Dongxu Wang, Zhiquan Liu, Haobin Yao, Yang Hao, Lina Zhou, Jian Du, Yixin Zhu, Yuxin Xu, Guodong Wang, Yuning Song, Zhanjun Li
Parthenogenetically activated oocytes cannot develop to term in mammals due to lack of paternal gene expression. Disruption of imprinted gene expression and DNA methylation status in parthenogenetic fetuses has been reported in mice and pigs, but not in rabbits. In this study, the genomic imprinting status of the paternally expressed genes Neuronatin (NNAT), Nucleosome assembly protein 1-like 5 (NAP1L5), and Makorin ring finger protein 3 (MKRN3) was compared between rabbit parthenogenetic (PA) and normally fertilized fetuses (Con) using quantitative real-time PCR (qRT-PCR) and bisulfite sequencing PCR (BSP)...
May 16, 2017: Gene
https://www.readbyqxmd.com/read/28525579/modulation-of-cyclobutane-thymine-photodimer-formation-in-t11-tracts-in-rotationally-phased-nucleosome-core-particles-and-dna-minicircles
#3
Kesai Wang, John-Stephen A Taylor
Cyclobutane pyrimidine dimers (CPDs) are DNA photoproducts linked to skin cancer, whose mutagenicity depends in part on their frequency of formation and deamination. Nucleosomes modulate CPD formation, favoring outside facing sites and disfavoring inward facing sites. A similar pattern of CPD formation in protein-free DNA loops suggests that DNA bending causes the modulation in nucleosomes. To systematically study the cause and effect of nucleosome structure on CPD formation and deamination, we have developed a circular permutation synthesis strategy for positioning a target sequence at different superhelix locations (SHLs) across a nucleosome in which the DNA has been rotationally phased with respect to the histone octamer by TG motifs...
May 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28523540/rubinstein-taybi-syndrome-and-epigenetic-alterations
#4
Edward Korzus
Rubinstein-Taybi syndrome (RSTS) is a rare genetic disorder in humans characterized by growth and psychomotor delay, abnormal gross anatomy, and mild to severe mental retardation (Rubinstein and Taybi, Am J Dis Child 105:588-608, 1963, Hennekam et al., Am J Med Genet Suppl 6:56-64, 1990). RSTS is caused by de novo mutations in epigenetics-associated genes, including the cAMP response element-binding protein (CREBBP), the gene-encoding protein referred to as CBP, and the EP300 gene, which encodes the p300 protein, a CBP homologue...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28522692/mitotic-chromosome-assembly-despite-nucleosome-depletion-in-xenopus-egg-extracts
#5
Keishi Shintomi, Fukashi Inoue, Hiroshi Watanabe, Keita Ohsumi, Miho Ohsugi, Tatsuya Hirano
The nucleosome is the fundamental structural units of eukaryotic chromatin. During mitosis, duplicated nucleosome fibers are organized into a pair of rod-shaped structures (chromatids) within a mitotic chromosome. However, it remains unclear whether nucleosome assembly is indeed an essential prerequisite for mitotic chromosome assembly. Here, we combined mouse sperm nuclei and Xenopus cell-free egg extracts depleted of the histone chaperone Asf1 and found that chromatid-like structures could be assembled even in the near-absence of nucleosomes...
May 18, 2017: Science
https://www.readbyqxmd.com/read/28520954/h2b-ubiquitylation-and-the-histone-chaperone-asf1-cooperatively-mediate-the-formation-and-maintenance-of-heterochromatin-silencing
#6
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/28520399/an-immunofluorescence-imaging-strategy-for-evaluation-of-the-accessibility-of-dna-5-hydroxymethylcytosine-in-chromatins
#7
Shangwei Zhong, Zhe Li, Ting Jiang, Xiangjun Li, Hailin Wang
DNA 5-hydroxymethylcytosine (5hmC) is an important epigenetic modification found in various mammalian cells. Immunofluorescence imaging analysis essentially provides visual pictures to the abundance and distribution of DNA 5hmC in single cells. However, nuclear DNA is usually wrapped around nucleosomes and packaged into chromatins, and further bound with many functional proteins. These physiologically relevant events would generate barriers to the anti-5hmC antibody to selectively recognize 5hmC in DNA. By taking advantage of these naturally generated barriers, here we present a strategy to evaluate the accessibility of DNA 5hmC in chromatins in situ...
May 18, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28515797/circulating-nucleosomes-as-new-blood-based-biomarkers-for-detection-of-colorectal-cancer
#8
Jean-François Rahier, Anne Druez, Laurence Faugeras, Jean-Paul Martinet, Myriam Géhénot, Eléonore Josseaux, Marielle Herzog, Jake Micallef, Fabienne George, Monique Delos, Thierry De Ronde, Abdenor Badaoui, Lionel D'Hondt
BACKGROUND: Colonoscopy is currently widely accepted as the gold standard for detection of colorectal cancer (CRC) providing detection of up to 95% of pre-cancerous lesions during the procedure. However, certain limitations exist in most countries including cost and access to the procedure. Moreover, colonoscopy is an invasive technique with risk inherent to the endoscopic procedure. For this reason, alternative screening tests, in particular, fecal occult blood-based tests, have been widely adopted for frontline screening...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28515491/the-emerging-field-of-epigenetics-in-neurodegeneration-and-neuroprotection
#9
REVIEW
Jee-Yeon Hwang, Kelly A Aromolaran, R Suzanne Zukin
Epigenetic mechanisms - including DNA methylation, histone post-translational modifications and changes in nucleosome positioning - regulate gene expression, cellular differentiation and development in almost all tissues, including the brain. In adulthood, changes in the epigenome are crucial for higher cognitive functions such as learning and memory. Striking new evidence implicates the dysregulation of epigenetic mechanisms in neurodegenerative disorders and diseases. Although these disorders differ in their underlying causes and pathophysiologies, many involve the dysregulation of restrictive element 1-silencing transcription factor (REST), which acts via epigenetic mechanisms to regulate gene expression...
May 18, 2017: Nature Reviews. Neuroscience
https://www.readbyqxmd.com/read/28514650/the-ino80-complex-removes-h2a-z-to-promote-presynaptic-filament-formation-during-homologous-recombination
#10
Claudio A Lademann, Jörg Renkawitz, Boris Pfander, Stefan Jentsch
The INO80 complex (INO80-C) is an evolutionarily conserved nucleosome remodeler that acts in transcription, replication, and genome stability. It is required for resistance against genotoxic agents and is involved in the repair of DNA double-strand breaks (DSBs) by homologous recombination (HR). However, the causes of the HR defect in INO80-C mutant cells are controversial. Here, we unite previous findings using a system to study HR with high spatial resolution in budding yeast. We find that INO80-C has at least two distinct functions during HR-DNA end resection and presynaptic filament formation...
May 16, 2017: Cell Reports
https://www.readbyqxmd.com/read/28512350/mechanisms-of-action-and-regulation-of-atp-dependent-chromatin-remodelling-complexes
#11
REVIEW
Cedric R Clapier, Janet Iwasa, Bradley R Cairns, Craig L Peterson
Cells utilize diverse ATP-dependent nucleosome-remodelling complexes to carry out histone sliding, ejection or the incorporation of histone variants, suggesting that different mechanisms of action are used by the various chromatin-remodelling complex subfamilies. However, all chromatin-remodelling complex subfamilies contain an ATPase-translocase 'motor' that translocates DNA from a common location within the nucleosome. In this Review, we discuss (and illustrate with animations) an alternative, unifying mechanism of chromatin remodelling, which is based on the regulation of DNA translocation...
May 17, 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/28507061/rnf8-mediates-histone-h3-ubiquitylation-and-promotes-glycolysis-and-tumorigenesis
#12
Yan Xia, Weiwei Yang, Ming Fa, Xinjian Li, Yugang Wang, Yuhui Jiang, Yanhua Zheng, Jong-Ho Lee, Jing Li, Zhimin Lu
Disassembly of nucleosomes in which genomic DNA is packaged with histone regulates gene expression. However, the mechanisms underlying nucleosome disassembly for gene expression remain elusive. We show here that epidermal growth factor receptor activation results in the binding of the RNF8 forkhead-associated domain to pyruvate kinase M2-phosphorylated histone H3-T11, leading to K48-linked polyubiquitylation of histone H3 at K4 and subsequent proteasome-dependent protein degradation. In addition, H3 polyubiquitylation induces histone dissociation from chromatin, nucleosome disassembly, and binding of RNA polymerase II to MYC and CCND1 promoter regions for transcription...
May 15, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28506460/mechanisms-of-ubiquitin-nucleosome-recognition-and-regulation-of-53bp1-chromatin-recruitment-by-rnf168-169-and-rad18
#13
Qi Hu, Maria Victoria Botuyan, Gaofeng Cui, Debiao Zhao, Georges Mer
The protein 53BP1 plays a central regulatory role in DNA double-strand break repair. 53BP1 relocates to chromatin by recognizing RNF168-mediated mono-ubiquitylation of histone H2A Lys15 in the nucleosome core particle dimethylated at histone H4 Lys20 (NCP-ubme). 53BP1 relocation is terminated by ubiquitin ligases RNF169 and RAD18 via unknown mechanisms. Using nuclear magnetic resonance (NMR) spectroscopy and biochemistry, we show that RNF169 bridges ubiquitin and histone surfaces, stabilizing a pre-existing ubiquitin orientation in NCP-ubme to form a high-affinity complex...
May 18, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28500727/biological-function-and-histone-recognition-of-family-iv-bromodomain-containing-proteins
#14
Jonathan T Lloyd, Karen C Glass
Bromodomain proteins function as epigenetic readers that recognize acetylated histone tails to facilitate the transcription of target genes. There are approximately 60 known human bromodomains, which are divided into 8 sub-families based on structural conservation. The bromodomain-containing proteins in family IV include 7 members (BRPF1, BRPF2, BRPF3, BRD7, BRD9, ATAD2 and ATAD2b). The bromodomains of each of these proteins recognize and bind acetyllysine residues on histone tails protruding from the nucleosome...
May 13, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28500048/insight-into-the-recent-genome-duplication-of-the-halophilic-yeast-hortaea-werneckii-combining-an-improved-genome-with-gene-expression-and-chromatin-structure
#15
Sunita Sinha, Stephane Flibotte, Mauricio Niera, Sean Formby, Ana Plemenitaš, Nina Gunde Cimerman, Metka Lenassi, Cene Gostinčar, Jason E Stajich, Corey Nislow
Extremophilic organisms demonstrate the flexibility and adaptability of basic biological processes by highlighting how cell physiology adapts to environmental extremes. Few eukaryotic extremophiles have been well studied and only a small number are amenable to laboratory cultivation and manipulation. A detailed characterisation of the genome architecture of such organisms is important to illuminate how they adapt to environmental stresses. One excellent example of a fungal extremophile is the halophile Hortaea werneckii (Pezizomycotina; Dothideomycetes, Capnodiales), a yeast-like fungus able to thrive at near-saturating concentrations of sodium chloride and which is also tolerant to both UV irradiation and desiccation...
May 12, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28499038/functional-characterization-and-architecture-of-recombinant-yeast-swr1-histone-exchange-complex
#16
Chia-Liang Lin, Yuriy Chaban, David M Rees, Elizabeth A McCormack, Lorraine Ocloo, Dale B Wigley
We have prepared recombinant fourteen subunit yeast SWR1 complex from insect cells using a modified MultiBac system. The 1.07 MDa recombinant protein complex has histone-exchange activity. Full exchange activity is realized with a single SWR1 complex bound to a nucleosome. We also prepared mutant complexes that lack a variety of subunits or combinations of subunits and these start to reveal roles for some of these subunits as well as indicating interactions between them in the full complex. Complexes containing a series of N-terminally and C-terminally truncated Swr1 subunits reveal further details about interactions between subunits as well as their binding sites on the Swr1 subunit...
May 12, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28498449/bioinformatic-analysis-of-the-effects-and-mechanisms-of-decitabine-and-cytarabine-on-acute-myeloid-leukemia
#17
Shiyong Zhou, Pengfei Liu, Huilai Zhang
Acute myeloid leukemia (AML) is a frequently occurring malignant disease of the blood and may result from a variety of genetic disorders. The present study aimed to identify the underlying mechanisms associated with the therapeutic effects of decitabine and cytarabine on AML, using microarray analysis. The microarray datasets GSE40442 and GSE40870 were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and differentially methylated sites were identified in AML cells treated with decitabine compared with those treated with cytarabine via the Linear Models for Microarray Data package, following data pre‑processing...
May 12, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28495586/solid-phase-synthesis-of-highly-repetitive-chromatin-assembly-templates
#18
Melissa J Blacketer, Margaret K Gannon, Isaac A Young, Michael A Shogren-Knaak
DNA templates for assembling chromatin model systems typically consist of numerous repeats of nucleosome positioning sequences, making their synthesis challenging. Here we describe a solid-phase strategy for generating such templates using sequential enzymatic ligation of DNA monomers. Using single nucleosome site monomers, we can either generate a twelve-nucleosome site target, or systematically access intermediate-sized templates. Using twelve nucleosome positioning site monomers, longer templates can be generated...
May 8, 2017: Analytical Biochemistry
https://www.readbyqxmd.com/read/28490494/structural-basis-for-spumavirus-gag-tethering-to-chromatin
#19
Paul Lesbats, Erik Serrao, Daniel P Maskell, Valerie E Pye, Nicola O'Reilly, Dirk Lindemann, Alan N Engelman, Peter Cherepanov
The interactions between a retrovirus and host cell chromatin that underlie integration and provirus expression are poorly understood. The prototype foamy virus (PFV) structural protein GAG associates with chromosomes via a chromatin-binding sequence (CBS) located within its C-terminal region. Here, we show that the PFV CBS is essential and sufficient for a direct interaction with nucleosomes and present a crystal structure of the CBS bound to a mononucleosome. The CBS interacts with the histone octamer, engaging the H2A-H2B acidic patch in a manner similar to other acidic patch-binding proteins such as herpesvirus latency-associated nuclear antigen (LANA)...
May 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28489565/motifs-in-the-amino-terminus-of-cenp-a-are-required-for-its-accumulation-within-the-nucleus-and-at-the-centromere
#20
Ruiqi Jing, Jiajie Xi, Ye Leng, Wen Chen, Guiying Wang, Wenwen Jia, Jiuhong Kang, Songcheng Zhu
Centromere protein A (CENP-A) is a variant of core histone H3 that marks the centromere's location on the chromosome. The mechanisms that target the protein to the nucleus and the centromere have not been defined. In this study, we found that deletion of the first 53 but not the first 29 residues of CENP-A from the amino-terminus, resulted in its cytoplasmic localization. Two motifs, R42R43R44 and K49R52K53K56, which are reported to be required for DNA contact in the centromere nucleosome, were found to be critical for CENP-A nuclear accumulation...
April 18, 2017: Oncotarget
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