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https://www.readbyqxmd.com/read/28220502/variations-on-a-nucleosome-theme-the-structural-basis-of-centromere-function
#1
Olga Moreno-Moreno, Mònica Torras-Llort, Fernando Azorín
The centromere is a specialized chromosomal structure that dictates kinetochore assembly and, thus, is essential for accurate chromosome segregation. Centromere identity is determined epigenetically by the presence of a centromere-specific histone H3 variant, CENP-A, that replaces canonical H3 in centromeric chromatin. Here, we discuss recent work by Roulland et al. that identifies structural elements of the nucleosome as essential determinants of centromere function. In particular, CENP-A nucleosomes have flexible DNA ends due to the short αN helix of CENP-A...
February 21, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28211081/h3f3a-mutation-in-giant-cell-tumour-of-the-bone-is-detected-by-immunohistochemistry-using-a-monoclonal-antibody-against-the-g34w-mutated-site-of-the-histone-h3-3-variant
#2
Julian Lüke, Alexandra von Baer, Jordan Schreiber, Christoph Lübbehüsen, Thomas Breining, Kevin Mellert, Ralf Marienfeld, Markus Schultheiss, Peter Möller, Thomas Fe Barth
AIMS: Giant cell tumour of bone (GCTB) is a neoplasm predominantly of long bones characterised by the H3F3A mutation G34W. Conventional diagnostic is challenged by the tumour's giant cell-rich morphology, which overlaps with other giant cell containing lesions of the bone. Recently, a monoclonal antibody specific for the H3F3A mutation has been generated. Our aim was to test this antibody on a cohort of giant cell containing lesions. METHODS AND RESULTS: We used the antibody for analysis of 22 H3F3A-mutated GCTB, including two patients with recurrences; for comparison we analysed a cohort of 36 H3F3A-wild-type giant cell-rich lesions of the bone and soft tissue, containing one brown tumour, six aneurysmal bone cysts, six chondroblastomas, five non-ossifying-fibromas, two fibrous dysplasias, nine tenosynovial giant cell tumours, one giant cell-rich sarcoma and six osteosarcomas...
February 17, 2017: Histopathology
https://www.readbyqxmd.com/read/28193886/improved-regulatory-element-prediction-based-on-tissue-specific-local-epigenomic-signatures
#3
Yupeng He, David U Gorkin, Diane E Dickel, Joseph R Nery, Rosa G Castanon, Ah Young Lee, Yin Shen, Axel Visel, Len A Pennacchio, Bing Ren, Joseph R Ecker
Accurate enhancer identification is critical for understanding the spatiotemporal transcriptional regulation during development as well as the functional impact of disease-related noncoding genetic variants. Computational methods have been developed to predict the genomic locations of active enhancers based on histone modifications, but the accuracy and resolution of these methods remain limited. Here, we present an algorithm, regulatory element prediction based on tissue-specific local epigenetic marks (REPTILE), which integrates histone modification and whole-genome cytosine DNA methylation profiles to identify the precise location of enhancers...
February 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28193539/dimeric-but-not-monomeric-%C3%AE-lactalbumin-potentiates-apoptosis-by-up-regulation-of-atf3-and-reduction-of-histone-deacetylase-activity-in-primary-and-immortalised-cells
#4
Julie A Sharp, Amelia J Brennan, Galina Polekhina, David B Ascher, Christophe Lefevre, Kevin R Nicholas
α-lactalbumin is a protein of dual function found in milk of most mammals. α-lactalbumin binds β-1,4-galactosyltransferase to form the regulatory subunit for lactose synthesis and has also been shown to cause cell death. This study shows, for the first time, that α-lactalbumin isolated in a rare 28kDa dimeric form induces cell death, while 14kDa monomeric α-lactalbumin is inactive. In contrast to the casein derived and chemically induced α-lactalbumin variants, MAL and HAMLET/BAMLET, the effects of 28kDa α-lactalbumin are calcium independent and, unlike MAL and HAMLET, 28kDa α-lactalbumin dimer causes cell death of primary mammary cells and a variety of immortalised cell lines, which are committed to cell death pathways within 1-4h of exposure...
February 10, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28192606/metformin-alleviates-aging-cellular-phenotypes-in-hutchinson-gilford-progeria-syndrome-dermal-fibroblasts
#5
Seul-Ki Park, Ok Sarah Shin
Metformin is a popular antidiabetic biguanide, which has been considered as a candidate drug for cancer treatment and aging prevention. Hutchinson-Gilford progeria syndrome (HGPS) is a devastating disease characterized by premature aging and severe age-associated complications leading to death. The effects of metformin on HGPS dermal fibroblasts remain largely undefined. In this study, we investigated whether metformin could exert a beneficial effect on nuclear abnormalities and delay senescence in fibroblasts derived from HGPS patients...
February 13, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28188343/mll5-kmt2e-structure-function-and-clinical-relevance
#6
REVIEW
Xiaoming Zhang, Wisna Novera, Yan Zhang, Lih-Wen Deng
The mixed lineage leukemia (MLL) family of genes, also known as the lysine N-methyltransferase 2 (KMT2) family, are homologous to the evolutionarily conserved trithorax group that plays critical roles in the regulation of homeotic gene (HOX) expression and embryonic development. MLL5, assigned as KMT2E on the basis of its SET domain homology, was initially categorized under MLL (KMT2) family together with other six SET methyltransferase domain proteins (KMT2A-2D and 2F-2G). However, emerging evidence suggests that MLL5 is distinct from the other MLL (KMT2) family members, and the protein it encodes appears to lack intrinsic histone methyltransferase (HMT) activity towards histone substrates...
February 10, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28188183/variants-of-the-sir4-coiled-coil-domain-improve-binding-to-sir3-for-heterochromatin-formation-in-saccharomyces-cerevisiae
#7
Anke Samel, Adam Rudner, Ann E Ehrenhofer-Murray
Heterochromatin formation in the yeast Saccharomyces cerevisiae is characterized by the assembly of the Silent Information Regulator (SIR) complex, which consists of the histone deacetylase Sir2 and the structural components Sir3 and Sir4 and binds to unmodified nucleosomes to provide gene silencing. Sir3 contains an AAA(+) ATPase-like domain, and mutations in an exposed loop on the surface of this domain abrogate Sir3 silencing function in vivo as well in vitro binding to the Sir2/ Sir4 subcomplex. Here, we found that the removal of a single methyl group in the C-terminal coiled-coil domain (mutation T1314S) of Sir4 was sufficient to restore silencing at the silent mating-type loci HMR and HML to a Sir3 version with a mutation in this loop...
February 10, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28177878/whole-genome-sequencing-identifies-new-genetic-alterations-in-meningiomas
#8
Mei Tang, Heng Wei, Lu Han, Jiaojiao Deng, Yuelong Wang, Meijia Yang, Yani Tang, Gang Guo, Liangxue Zhou, Aiping Tong
The major known genetic contributor to meningioma formation was NF2, which is disrupted by mutation or loss in about 50% of tumors. Besides NF2, several recurrent driver mutations were recently uncovered through next-generation sequencing. Here, we performed whole-genome sequencing across 7 tumor-normal pairs to identify somatic genetic alterations in meningioma. As a result, Chromatin regulators, including multiple histone members, histone-modifying enzymes and several epigenetic regulators, are the major category among all of the identified copy number variants and single nucleotide variants...
February 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28177753/histone-h3-3-regulates-mitotic-progression-in-mouse-embryonic-fibroblasts
#9
Aysegul Ors, Christophe Papin, Bertrand Favier, Yohan Roulland, Defne Dalkara, Mehmet Ozturk, ALi Hamiche, Stefan Dimitrov, Kiran Padmanabhan
H3.3 is a histone variant, which marks transcription start sites as well as telomeres and heterochromatic sites on the genome. H3.3 presence is thought to positively correlate with transcriptional status of its target genes. Using a conditional genetic strategy against H3.3B combined with short hairpin RNAs against H3.3A, we essentially depleted all H3.3 gene expression in mouse embryonic fibroblasts. Following nearly complete loss of H3.3 in cells, our transcriptomic analyses show very little impact on global gene expression as well as on histone variant H2A...
February 1, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28176832/epro-clearsee-a-simple-immunohistochemical-method-that-does-not-require-sectioning-of-plant-samples
#10
Kiyotaka Nagaki, Naoki Yamaji, Minoru Murata
Investigations into the epigenetic status of individual cells within tissues can produce both epigenetic data for different cell types and positional information of the cells. Thus, these investigations are important for understanding the intra- and inter-cellular control systems of developmental and environmental responses in plants. However, a simple method to detect epigenetic modifications of individual cells in plant tissues is not yet available because detection of the modifications requires immunohistochemistry using specific antibodies...
February 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28167779/integrity-of-the-human-centromere-dna-repeats-is-protected-by-cenp-a-cenp-c-and-cenp-t
#11
Simona Giunta, Hironori Funabiki
Centromeres are highly specialized chromatin domains that enable chromosome segregation and orchestrate faithful cell division. Human centromeres are composed of tandem arrays of α-satellite DNA, which spans up to several megabases. Little is known about the mechanisms that maintain integrity of the long arrays of α-satellite DNA repeats. Here, we monitored centromeric repeat stability in human cells using chromosome-orientation fluorescent in situ hybridization (CO-FISH). This assay detected aberrant centromeric CO-FISH patterns consistent with sister chromatid exchange at the frequency of 5% in primary tissue culture cells, whereas higher levels were seen in several cancer cell lines and during replicative senescence...
February 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28163244/colonic-transcriptional-response-to-1%C3%AE-25-oh-2-vitamin-d3-in-african-and-european-americans
#12
Dereck Alleyne, David B Witonsky, Brandon Mapes, Shigeki Nakagome, Meredith Sommars, Ellie Hong, Katy A Muckala, Anna Di Rienzo, Sonia S Kupfer
Colorectal cancer (CRC) is a significant health burden especially among African Americans (AA). Epidemiological studies have correlated low serum vitamin D with CRC risk, and, while hypovitaminosis D is more common and more severe in AA, the mechanisms by which vitamin D modulates CRC risk and how these differ by race are not well understood. Active vitamin D (1α,25(OH)2D3) has chemoprotective effects primarily through transcriptional regulation of target genes in the colon. We hypothesized that transcriptional response to 1α,25(OH)2D3 differs between AA and European Americans (EA) irrespective of serum vitamin D and that regulatory variants could impact transcriptional response...
February 3, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28163185/genomic-characterization-and-dynamic-methylation-of-promoter-facilitates-transcriptional-regulation-of-h2a-variants-h2a-1-and-h2a-2-in-various-pathophysiological-states-of-hepatocyte
#13
Monica Tyagi, Divya Reddy, Sanjay Gupta
Differential expression of homomorphous variants of H2A family of histone H2A.1 and H2A.2 have been associated with hepatocellular carcinoma and maintenance of undifferentiated state of hepatocyte. However, not much is known about the transcriptional regulation of these H2A variants. The current study revealed the presence of 43bp 5'-regulatory region upstream of translation start site and a 26bp 3' stem loop conserved region for both the H2A.1 and H2A.2 variants. However, alignment of both H2A.1 and H2A.2 5'-untranslated region (UTR) sequences revealed no significant degree of homology between them despite the coding exon being very similar amongst the variants...
February 3, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28161275/epigenetic-interplay-at-the-%C3%AE-globin-locus
#14
REVIEW
Wei Shern Lee, Bradley McColl, Jovana Maksimovic, Jim Vadolas
During development, the α- and β-globin genes exhibit a highly conserved pattern of expression, giving rise to several developmental stage-specific hemoglobin variants. Networks of regulatory proteins interact with epigenetic complexes to regulate DNA accessibility and histone modifications, thereby determining appropriate patterns of globin gene expression. In this review, we focus on recent advances in the understanding of the molecular mechanisms that underpin globin gene expression, focusing on multi-subunit regulatory complexes that bind to specific regions of DNA to orchestrate globin gene transcription throughout development...
February 1, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28157715/combined-use-of-irinotecan-with-histone-deacetylase-inhibitor-belinostat-could-cause-severe-toxicity-by-inhibiting-sn-38-glucuronidation-via-ugt1a1
#15
Lingzhi Wang, Chong En Linus Chan, Andrea Li-Ann Wong, Fang Cheng Wong, Siew Woon Lim, Arunachalam Chinnathambi, Sulaiman Ali Alharbi, Lawrence Soon-U Lee, Ross Soo, Wei Peng Yong, Soo Chin Lee, Paul Chi-Lui Ho, Gautam Sethi, Boon Cher Goh
SN-38, the active metabolite of irinotecan, and histone deacetylase inhibitors (HDACis) such as belinostat, vorinostat and panobinostat, have all been shown to be deactivated by glucuronidation via UGTs. Since they all compete for UGTs for deactivation, we aimed to investigate the inhibitory effect of various HDACis on the glucuronidation of SN-38. This inhibitory effect was determined by measuring the formation rate of SN-38 glucuronide after SN-38 incubation with human recombinant UGT1A isoforms (1A1, 1A6, 1A7 and 1A9) and pooled human liver microsomes (HLM, wild type, UGT1A1*1*28 and UGT1A1*28*28 allelic variants), with and without HDACis...
February 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28155643/identification-of-recurrent-combinatorial-patterns-of-chromatin-modifications-at-promoters-across-various-tissue-types
#16
Nan Meng, Raghu Machiraju, Kun Huang
BACKGROUND: Identification and analysis of recurrent combinatorial patterns of multiple chromatin modifications provide invaluable information for understanding epigenetic regulations. Furthermore, as more data becomes available, it is computationally expensive and unnecessary to study combinatorial patterns of all modifications. METHODS: A novel framework is proposed to investigate recurrent combinatorial patterns of a subset of quantitatively selected chromatin modifications...
December 23, 2016: BMC Bioinformatics
https://www.readbyqxmd.com/read/28155083/the-long-zinc-finger-domain-of-prdm9-forms-a-highly-stable-and-long-lived-complex-with-its-dna-recognition-sequence
#17
Yasmin Striedner, Theresa Schwarz, Thomas Welte, Andreas Futschik, Ulrich Rant, Irene Tiemann-Boege
PR domain containing protein 9 (PRDM9) is a meiosis-specific, multi-domain protein that regulates the location of recombination hotspots by targeting its DNA recognition sequence for double-strand breaks (DSBs). PRDM9 specifically recognizes DNA via its tandem array of zinc fingers (ZnFs), epigenetically marks the local chromatin by its histone methyltransferase activity, and is an important tether that brings the DNA into contact with the recombination initiation machinery. A strong correlation between PRDM9-ZnF variants and specific DNA motifs at recombination hotspots has been reported; however, the binding specificity and kinetics of the ZnF domain are still obscure...
February 2, 2017: Chromosome Research
https://www.readbyqxmd.com/read/28151037/differential-deposition-of-h2a-z-in-rice-seedling-tissue-during-the-day-night-cycle
#18
Kang Zhang, Wenying Xu, Chunchao Wang, Xin Yi, Zhen Su
Chromatin structure has an important role in modulating gene expression. The incorporation of histone variants into the nucleosome leads to important changes in the chromatin structure. The histone variant H2A.Z is highly conserved between different species of fungi, animals, and plants. However, dynamic changes to H2A.Z in rice have been reported during the day-night cycle. In this study, we generated genome wide maps of H2A.Z for day and night time harvested seedling tissues by combining chromatin immunoprecipitation and high-throughput sequencing...
February 2, 2017: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/28144029/variants-of-core-histones-and-their-roles-in-cell-fate-decisions-development-and-cancer
#19
REVIEW
Marcus Buschbeck, Sandra B Hake
Histone variants endow chromatin with unique properties and show a specific genomic distribution that is regulated by specific deposition and removal machineries. These variants - in particular, H2A.Z, macroH2A and H3.3 - have important roles in early embryonic development, and they regulate the lineage commitment of stem cells, as well as the converse process of somatic cell reprogramming to pluripotency. Recent progress has also shed light on how mutations, transcriptional deregulation and changes in the deposition machineries of histone variants affect the process of tumorigenesis...
February 1, 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/28138144/chromatin-dynamics-during-the-cell-cycle-at-centromeres
#20
REVIEW
Sebastian Müller, Geneviève Almouzni
Centromeric chromatin undergoes major changes in composition and architecture during each cell cycle. These changes in specialized chromatin facilitate kinetochore formation in mitosis to ensure proper chromosome segregation. Thus, proper orchestration of centromeric chromatin dynamics during interphase, including replication in S phase, is crucial. We provide the current view concerning the centromeric architecture associated with satellite repeat sequences in mammals and its dynamics during the cell cycle...
January 31, 2017: Nature Reviews. Genetics
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