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Histone variants

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https://www.readbyqxmd.com/read/29785653/valproic-acid-treatment-response-in-vitro-is-determined-by-tp53-status-in-medulloblastoma
#1
Bruna Mascaro-Cordeiro, Indhira Dias Oliveira, Francine Tesser-Gamba, Lorena Favaro Pavon, Nasjla Saba-Silva, Sergio Cavalheiro, Patrícia Dastoli, Silvia Regina Caminada Toledo
PURPOSE: Histone deacetylate inhibitors (HDACi), as valproic acid (VA), have been reported to enhance efficacy and to prevent drug resistance in some tumors, including medulloblastoma (MB). In the present study, we investigated VA role, combined to cisplatin (CDDP) in cell viability and gene expression of MB cell lines. METHODS: Dose-response curve determined IC50 values for each treatment: (1) VA single, (2) CDDP single, and (3) VA and CDDP combined. Cytotoxicity and flow cytometry evaluated cell viability after exposure to treatments...
May 22, 2018: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/29785231/advantages-of-evaluating-%C3%AE-h2ax-induction-in-non-clinical-drug-development
#2
REVIEW
Shigeki Motoyama, Akira Takeiri, Kenji Tanaka, Asako Harada, Kaori Matsuzaki, Junko Taketo, Saori Matsuo, Etsuko Fujii, Masayuki Mishima
γH2AX, the phosphorylated form of a histone variant H2AX at Ser 139, is already widely used as a biomarker to research the fundamental biology of DNA damage and repair and to assess the risk of environmental chemicals, pollutants, radiation, and so on. It is also beginning to be used in the early non-clinical stage of pharmaceutical drug development as an in vitro tool for screening and for mechanistic studies on genotoxicity. Here, we review the available information on γH2AX-based test systems that can be used to develop drugs and present our own experience of practically applying these systems during the non-clinical phase of drug development...
2018: Genes and Environment: the Official Journal of the Japanese Environmental Mutagen Society
https://www.readbyqxmd.com/read/29784888/identification-of-brain-metastasis-genes-and-therapeutic-evaluation-of-histone-deacetylase-inhibitors-in-a-clinically-relevant-model-of-breast-cancer-brain-metastasis
#3
Soo-Hyun Kim, Richard P Redvers, Lap Hing Chi, Xiawei Ling, Andrew J Lucke, Robert C Reid, David P Fairlie, Ana Carolina Baptista Moreno Martin, Robin L Anderson, Delphine Denoyer, Normand Pouliot
Breast cancer brain metastasis remains largely incurable. While several mouse models have been developed to investigate the genes and mechanisms regulating breast cancer brain metastasis, these models often lack clinical relevance since they require the use of immune-compromised mice and/or are poorly metastatic to brain from the mammary gland. We describe the development and characterisation of an aggressive brain metastatic variant of the 4T1 syngeneic model (4T1Br4) that spontaneously metastasises to multiple organs, but is selectively more metastatic to the brain from the mammary gland than parental 4T1 tumours...
May 21, 2018: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29780501/a-bi-terminal-protein-ligation-strategy-to-probe-chromatin-structure-during-dna-damage
#4
Sinan Kilic, Iuliia Boichenko, Carolin C Lechner, Beat Fierz
The cellular response to DNA damage results in a signaling cascade that primes chromatin for repair. Combinatorial post-translational modifications (PTMs) play an important role in this process by altering the physical properties of chromatin and recruiting downstream factors. One key signal integrator is the histone variant H2A.X, which is phosphorylated at a C-terminal serine (S139ph), and ubiquitylated within its N-terminal tail at lysines 13 and 15 (K13/15ub). How these PTMs directly impact chromatin structure and thereby facilitate DNA repair is not well understood...
April 21, 2018: Chemical Science
https://www.readbyqxmd.com/read/29771329/regulation-of-the-neuropathy-associated-pmp22-gene-by-a-distal-super-enhancer
#5
Harrison Pantera, John J Moran, Holly A Hung, Evgenia Pak, Amalia Dutra, John Svaren
Peripheral nerve myelination is adversely affected in the most common form of the hereditary peripheral neuropathy called Charcot-Marie-Tooth Disease. This form, classified as CMT1A, is caused by a 1.4 Mb duplication on chromosome 17, which includes the abundantly expressed Schwann cell myelin gene, Peripheral Myelin Protein 22 (PMP22). This is one of the most common copy number variants causing neurological disease. Overexpression of Pmp22 in rodent models recapitulates several aspects of neuropathy, and reduction of Pmp22 in such models results in amelioration of the neuropathy phenotype...
May 16, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29764984/parallel-evolution-of-common-allelic-variants-confers-flowering-diversity-in-capsella-rubella
#6
Li Yang, Hui-Na Wang, Xing-Hui Hou, Yu-Pan Zou, Ting-Shen Han, Xiao-Min Niu, Jie Zhang, Zhong Zhao, Marco Todesco, Sureshkumar Balasubramanian, Ya-Long Guo
Flowering time is an adaptive life history trait. Capsella rubella, a close relative of Arabidopsis thaliana and a young species, displays extensive variation for flowering time but low standing genetic variation due to an extreme bottleneck event, providing an excellent opportunity to understand how phenotypic diversity can occur with a limited initial gene pool. Here, we demonstrate that common allelic variation and parallel evolution at the FLC locus confer variation in flowering time in C. rubella. We show that two overlapping deletions in the 5' UTR region of C...
May 15, 2018: Plant Cell
https://www.readbyqxmd.com/read/29760389/aurora-a-dependent-cenp-a-phosphorylation-at-inner-centromeres-protects-bioriented-chromosomes-against-cohesion-fatigue
#7
Grégory Eot-Houllier, Laura Magnaghi-Jaulin, Géraldine Fulcrand, François-Xavier Moyroud, Solange Monier, Christian Jaulin
Sustained spindle tension applied to sister centromeres during mitosis eventually leads to uncoordinated loss of sister chromatid cohesion, a phenomenon known as "cohesion fatigue." We report that Aurora A-dependent phosphorylation of serine 7 of the centromere histone variant CENP-A (p-CENP-AS7) protects bioriented chromosomes against cohesion fatigue. Expression of a non-phosphorylatable version of CENP-A (CENP-AS7A) weakens sister chromatid cohesion only when sister centromeres are under tension, providing the first evidence of a regulated mechanism involved in protection against passive cohesion loss...
May 14, 2018: Nature Communications
https://www.readbyqxmd.com/read/29760313/detection-of-sirtuin-1-protein-expression-in-peripheral-blood-leukocytes-in-dogs
#8
Kuniko Yoshimura, Aya Matsuu, Kai Sasaki, Yasuyuki Momoi
Sirtuin-1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+ )-dependent histone deacetylase with a large number of protein substrates. It has attracted a lot of attention in association with extending lifespan. The objective of this study was to enable the evaluation of SIRT1 expression in peripheral blood mononuclear cells (PBMCs) from dogs by flow cytometry. Three transcript variants were amplified from PBMCs by reverse transcription PCR and the nucleotide sequences were analyzed. On the basis deduced amino acid sequence, a monoclonal antibody against human SIRT1, 1F3, was selected to detect canine SIRT1...
May 11, 2018: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/29760279/histone-h3k27-methylation-is-required-for-nhej-and-genome-stability-by-modulating-the-dynamics-of-fancd2-on-chromatin
#9
Ye Zhang, Jian-Feng Chang, Jin Sun, Lu Chen, Xiao-Mei Yang, Huan-Yin Tang, Yuan-Ya Jing, Xuan Kang, Zhi-Min He, Jun-Yu Wu, Hui-Min Wei, Da-Liang Wang, Rong-Gang Xu, Rui-Bao Zhu, Ying Shen, Shi-Yang Zeng, Chen Wang, Kui-Nan Liu, Yong Zhang, Zhi-Ying Mao, Ci-Zhong Jiang, Fang-Lin Sun
Dysregulation of homeostatic balance in di- and tri-methyl H3K27 levels or that caused by mis-sense mutations of histone H3 (H3K27M) was reported to be associated with various types of cancers. In this study, we found that reduction in H3K27me2/3 caused by H3.1K27M, a mutation of H3 variants found in DIPG patients, dramatically attenuated the presence of 53BP1 foci and NHEJ repair capability in HDF cells. H3.1K27M cells showed increased rates of genomic insertions/deletions (In/Dels) and copy number variations (CNVs), as well as augmented p53-dependent apoptotic cells...
May 14, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29753921/de-novo-loss-of-function-variants-of-ash1l-are-associated-with-an-emergent-neurodevelopmental-disorder
#10
Wei Shen, Patti Krautscheid, Audrey M Rutz, Pinar Bayrak-Toydemir, Sarah L Dugan
De novo variants of ASH1L, which encodes a histone methyltransferase, have been reported in a few patients with intellectual disability and autistic features. Here, we identified a novel de novo frame-shift variant, c.2422_2423delAAinsT which predicts p.(Lys808TyrfsTer40), in ASH1L in a patient with multiple congenital anomalies (MCA), fine motor developmental delay, learning difficulties, attention deficit hyperactivity disorder, sleep apnea, and scoliosis. This frame-shift variant is expected to result in loss-of-function...
May 10, 2018: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/29742439/norc-recruitment-by-h2a-x-deposition-at-rrna-gene-promoter-limits-embryonic-stem-cell-proliferation
#11
Boris Eleuteri, Sergi Aranda, Patrik Ernfors
Embryonic stem cells (ESCs) display an abbreviated cell cycle, resulting in a short doubling time and rapid proliferation. The histone variant H2A.X is critical for proliferation of stem cells, although mechanistic insights have remained obscure. Here, we show that H2A.X defines the rate of mouse ESC proliferation independently of the DNA damage response pathway, and it associates with three major chromatin-modifying complexes. Our functional and biochemical analyses demonstrate that H2A.X-associated factors mediate the H2A...
May 8, 2018: Cell Reports
https://www.readbyqxmd.com/read/29738831/histone-variant-h2a-z-antagonizes-the-positive-effect-of-the-transcriptional-activator-cpc1-to-regulate-catalase-3-expression-under-normal-and-oxidative-stress-conditions
#12
Qing Dong, Yajun Wang, Shaohua Qi, Kexin Gai, Qun He, Ying Wang
In eukaryotes, deposition of the histone variant H2A.Z into nucleosomes through the chromatin remodeling complex, SWR1, is a crucial step in modulating gene transcription. Recently, H2A.Z has been shown to control the expression of responsive genes, but the underlying mechanism of how H2A.Z responds to physiological stimuli is not well understood. Here, we reveal that, in Neurospora crassa, H2A.Z is a negative regulator of catalase-3 gene, which is responsible for resistance to oxidative stress. H2A.Z represses cat-3 gene expression through direct incorporation at cat-3 locus in a SWR1 complex dependent pathway...
May 5, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29717056/chromatin-immunoprecipitation-chip-analysis-of-protein-dna-interactions
#13
Tae Hoon Kim, Job Dekker
Here we describe chromatin immunoprecipitation (ChIP), a molecular approach that uses formaldehyde cross-linking to investigate genome structure and function. This approach allows us to determine the distribution of histone modifications (e.g., acetylation, methylation), the deposition of histone variants (H2AZ, H3.3, etc.), and the location of sequence-specific and general transcription factors. We introduce well-established ChIP-based methods that allow analysis of protein-DNA interactions in living cells...
May 1, 2018: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/29715312/a-catalog-of-potential-putative-functional-variants-in-psoriasis-genome-wide-association-regions
#14
Yan Lin, Lu Liu, Yujun Sheng, Changbing Shen, Xiaodong Zheng, Fusheng Zhou, Sen Yang, Xianyong Yin, Xuejun Zhang
Psoriasis is a common inflammatory skin disease, with considerable genetic contribution. Genome-wide association studies have successfully identified a number of genomic regions for the risk of psoriasis. However, it is challenging to pinpoint the functional causal variants and then further decipher the genetic mechanisms underlying each region. In order to prioritize potential functional causal variants within psoriasis susceptibility regions, we integrated the genetic association findings and functional genomic data publicly available, i...
2018: PloS One
https://www.readbyqxmd.com/read/29712835/histone-demethylase-jmjd1a-promotes-alternative-splicing-of-ar-variant-7-ar-v7-in-prostate-cancer-cells
#15
Lingling Fan, Fengbo Zhang, Songhui Xu, Xiaolu Cui, Arif Hussain, Ladan Fazli, Martin Gleave, Xuesen Dong, Jianfei Qi
Formation of the androgen receptor splicing variant 7 (AR-V7) is one of the major mechanisms by which resistance of prostate cancer to androgen deprivation therapy occurs. The histone demethylase JMJD1A (Jumonji domain containing 1A) functions as a key coactivator for AR by epigenetic regulation of H3K9 methylation marks. Here, we describe a role for JMJD1A in AR-V7 expression. While JMJD1A knockdown had no effect on full-length AR (AR-FL), it reduced AR-V7 levels in prostate cancer cells. Reexpression of AR-V7 in the JMJD1A-knockdown cells elevated expression of select AR targets and partially rescued prostate cancer cell growth in vitro and in vivo...
April 30, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29710702/sex-dependent-differences-in-spontaneous-autoimmunity-in-adult-3xtg-ad-mice
#16
Minesh Kapadia, M Firoz Mian, Bernadeta Michalski, Amber Azam, Donglai Ma, Patrick Salwierz, Adam Christopher, Elyse Rosa, Iva Zovkic, Paul Forsythe, Margaret Fahnestock, Boris Sakic
The triple-transgenic (3xTg-AD) mouse strain is a valuable model of Alzheimer's disease (AD) because it develops both amyloid-β (Aβ) and tau brain pathology. However, 1-year-old 3xTg-AD males no longer show plaques and tangles, yet early in life, they exhibit diverse signs of systemic autoimmunity. The current study aimed to address whether females, which exhibit more severe plaque/tangle pathology at 1 year of age, show similar autoimmune phenomena and if so, whether these immunological changes coincide with prodromal markers of AD pathology, markers of learning and memory formation and epigenetic markers of neurodegenerative disease...
April 25, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29706550/single-cell-chromatin-modification-profiling-reveals-increased-epigenetic-variations-with-aging
#17
Peggie Cheung, Francesco Vallania, Hayley C Warsinske, Michele Donato, Steven Schaffert, Sarah E Chang, Mai Dvorak, Cornelia L Dekker, Mark M Davis, Paul J Utz, Purvesh Khatri, Alex J Kuo
Post-translational modifications of histone proteins and exchanges of histone variants of chromatin are central to the regulation of nearly all DNA-templated biological processes. However, the degree and variability of chromatin modifications in specific human immune cells remain largely unknown. Here, we employ a highly multiplexed mass cytometry analysis to profile the global levels of a broad array of chromatin modifications in primary human immune cells at the single-cell level. Our data reveal markedly different cell-type- and hematopoietic-lineage-specific chromatin modification patterns...
April 21, 2018: Cell
https://www.readbyqxmd.com/read/29689274/the-mechanistic-effects-of-the-dioxonaphthoimidazolium-analog-ym155-in-renal-cell-carcinoma-cell-cycling-and-apoptosis
#18
Mei Yi Sim, Mei Lin Go, John Shyi Peng Yuen
AIM: To investigate the effect of dioxonaphthoimidazolium analog YM155 on cell cycle progression of the clear-cell variant of renal cell carcinoma (ccRCC). MAIN METHODS: Cell cycle analysis was performed using bromodeoxyuridine (BrdU) and PI, apoptosis initiation was monitored using Annexin V and proteins expression was determined using western immunoblotting. KEY FINDINGS: Here, we showed that YM155 activated stress-related molecules (histone H2AX, checkpoint kinases Chk1 and Chk2, p53) that mediate DNA damage checkpoint responses...
April 21, 2018: Life Sciences
https://www.readbyqxmd.com/read/29689253/histone-h3-3-g34-mutations-alter-histone-h3k36-and-h3k27-methylation-in-cis
#19
Leilei Shi, Jiejun Shi, Xiaobing Shi, Wei Li, Hong Wen
Histone H3 encoding genes, particularly H3F3A and H3F3B, the genes encoding the variant histone H3.3, are mutated at high frequency in pediatric brain and bone malignancies. Compared to the extensive stidues on K27M and K36M mutations, little is known about the mechanism of G34 mutations found in pediatric glioblastoma (GBM) or giant cell tumors of the bone (GCTB). Here we report that unlike the K27M or K36M that affect global histone methylation, the GCBT G34 mutations (G34L/W) only affect histone H3K36 and H3K27 methylation on the same mutated histone tails (in cis), a mechanism distinct from known histone mutations...
April 21, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29689243/whole-exome-sequencing-identifies-unique-mutations-and-copy-number-losses-in-calcifying-fibrous-tumor-of-the-pleura-report-of-three-cases-and-review-of-the-literature
#20
Mitra Mehrad, William A LaFramboise, Maureen A Lyons, Humberto E Trejo Bittar, Samuel A Yousem
Calcifying fibrous tumor of the pleura (CFTP) is a rare mesenchymal tumor of unknown pathogenesis. The diagnosis often requires exclusion of other common entities. Our aim was to determine if genomic changes were associated with CFTP that could contribute to mechanisms underlying tumorigenesis. Three cases of CFTP with their corresponding uninvolved control lung tissue were identified. Two patients were male, and one was female (age range: 21-32years). Tumors were multifocal in two cases and solitary in one...
April 21, 2018: Human Pathology
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