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histone variant

Thomas Lumley, Jennifer Brody, Gina Peloso, Alanna Morrison, Kenneth Rice
The sequence kernel association test (SKAT) is widely used to test for associations between a phenotype and a set of genetic variants that are usually rare. Evaluating tail probabilities or quantiles of the null distribution for SKAT requires computing the eigenvalues of a matrix related to the genotype covariance between markers. Extracting the full set of eigenvalues of this matrix (an n×n matrix, for n subjects) has computational complexity proportional to n3 . As SKAT is often used when n>104, this step becomes a major bottleneck in its use in practice...
June 22, 2018: Genetic Epidemiology
Sadaf Riaz, Zhenghong Sui
The nucleosomal organization of chromatin using histone proteins is a fundamental and ubiquitous feature of eukaryotic nuclei, with the major exception of dinoflagellates. Although a number of recent genomic and transcriptomic analysis have detected numerous histone genes in dinoflagellates, however, little is known about their expression. Here, we aimed to investigate expression pattern of histone genes under nutritional stress and an attempt was made to detect histone expression at protein level in Alexandrium pacificum ...
May 11, 2018: Journal of Microbiology and Biotechnology
Jin-Man Kim, Yonghwan Shin, Sunyoung Lee, Mi Yeong Kim, Vasu Punj, Hong-In Shin, Kyunghwan Kim, Jung-Min Koh, Daewon Jeong, Woojin An
Osteoclasts are multinuclear bone-resorbing cells that differentiate from hematopoietic precursor cells. Prostate cancer cells frequently spread to bone and secrete soluble signaling factors to accelerate osteoclast differentiation and bone resorption. However, processes and mechanisms that govern the expression of osteoclastogenic soluble factors secreted by prostate cancer cells are largely unknown. MacroH2A (mH2A) is a histone variant that replaces canonical H2A at designated genomic loci and establishes functionally distinct chromatin regions...
June 20, 2018: Oncogene
Carlo Maria Di Liegro, Gabriella Schiera, Italia Di Liegro
H1 linker histones are a class of DNA-binding proteins involved in the formation of supra-nucleosomal chromatin higher order structures. Eleven non-allelic subtypes of H1 are known in mammals, seven of which are expressed in somatic cells, while four are germ cell-specific. Besides having a general structural role, H1 histones also have additional epigenetic functions related to DNA replication and repair, genome stability, and gene-specific expression regulation. Synthesis of the H1 subtypes is differentially regulated both in development and adult cells, thus suggesting that each protein has a more or less specific function...
June 20, 2018: Genes
Prashanth Krishna Shastrula, Peder J Lund, Benjamin A Garcia, Susan M Janicki
The histone H3 variant, H3.3, is a highly conserved and dynamic regulator of chromatin organization.  Therefore, fully elucidating its nucleosome incorporation mechanisms is essential to understanding its functions in epigenetic inheritance.  We previously identified the RNase P protein subunit, Rpp29, as a repressor of H3.3 chromatin assembly.  Here, we use a biochemical assay to show that Rpp29 interacts with H3.3 through a sequence element in its own N-terminus, and we identify a novel interaction with histone H2B at an adjacent site...
June 19, 2018: Journal of Biological Chemistry
Matthew Bratkowski, Xin Yang, Xin Liu
Polycomb repressive complex 2 (PRC2) mediates trimethylation of histone H3K27 (H3K27me3), an epigenetic hallmark for repressed chromatin. Overactive mutants of the histone lysine methyltransferase subunit of PRC2, Ezh2, are found in various types of cancers. Pyridone-containing inhibitors such as GSK126 compete with S-adenosylmethionine (SAM) for Ezh2 binding and effectively inhibit PRC2 activity. PRC2 from the thermophilic fungus Chaetomium thermophilum (ct) is functionally similar to the human version in several regards and has the added advantage of producing high-resolution crystal structures, although inhibitor-bound structures of human or human/chameleon PRC2 are also available at up to 2...
June 14, 2018: Scientific Reports
Amanda R Wasylishen, Jeannelyn S Estrella, Vinod Pant, Gilda P Chau, Guillermina Lozano
Mutations in the death domain-associated protein (DAXX) have been recently identified in a substantial proportion of human pancreatic neuroendocrine tumors (PanNETs). Remarkably, however, little is known about the physiological role(s) of DAXX despite in vitro studies suggesting potential functions. Most prominently, and supported by tumor sequencing data, DAXX functions in concert with alpha thalassemia/mental retardation X-linked (ATRX) as a histone chaperone complex for the H3.3 variant. Studies have also identified potential roles in apoptosis, transcription, and negative regulation of the p53 tumor suppressor pathway...
June 14, 2018: Molecular Cancer Research: MCR
Lu-Chen Weng, Weihua Guan, Lyn M Steffen, James S Pankow, Nathan Pankratz, Ming-Huei Chen, Mary Cushman, Saonli Basu, Aaron R Folsom, Weihong Tang
INTRODUCTION: Data from epidemiological studies and clinical trials suggest an influence of dietary and circulating polyunsaturated fatty acids (PUFAs) on the hemostasis profile. Genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) related to plasma PUFAs levels. We aimed to investigate whether the SNPs related to plasma PUFAs levels were also associated with plasma levels of hemostatic variables. MATERIALS AND METHODS: We tested the associations between 9 PUFA-related SNPs and 6 hemostatic variables in 9035 European Americans (EAs) and 2702 African Americans (AAs) in the Atherosclerosis Risk in Communities (ARIC) Study...
June 1, 2018: Thrombosis Research
Chih-Chao Hsu, Dan Zhao, Jiejun Shi, Danni Peng, Haipeng Guan, Yuanyuan Li, Yaling Huang, Hong Wen, Wei Li, Haitao Li, Xiaobing Shi
The histone variant H2A.Z is essential for maintaining embryonic stem cell (ESC) identity in part by keeping developmental genes in a poised bivalent state. However, how H2A.Z is deposited into the bivalent domains remains unknown. In mammals, two chromatin remodeling complexes, Tip60/p400 and SRCAP, exchange the canonical histone H2A for H2A.Z in the chromatin. Here we show that Glioma Amplified Sequence 41 (Gas41), a shared subunit of the two H2A.Z-depositing complexes, functions as a reader of histone lysine acetylation and recruits Tip60/p400 and SRCAP to deposit H2A...
2018: Cell Discovery
Matthias Benoit, Lauriane Simon, Sophie Desset, Céline Duc, Sylviane Cotterell, Axel Poulet, Samuel Le Goff, Christophe Tatout, Aline V Probst
Developmental phase transitions are often characterized by changes in the chromatin landscape and heterochromatin reorganization. In Arabidopsis, clustering of repetitive heterochromatic loci into so-called chromocenters is an important determinant of chromosome organization in nuclear space. Here, we investigated the molecular mechanisms involved in chromocenter formation during the switch from a heterotrophic to a photosynthetically competent state during early seedling development. We characterized the spatial organization and chromatin features at centromeric and pericentromeric repeats and identified mutant contexts with impaired chromocenter formation...
June 13, 2018: New Phytologist
Jan Postberg, Franziska Jönsson, Patrick Philipp Weil, Aneta Bulic, Stefan Andreas Juranek, Hans-Joachim Lipps
BACKGROUND: During sexual reproduction in the unicellular ciliate Stylonychia somatic macronuclei differentiate from germline micronuclei. Thereby, programmed sequence reduction takes place, leading to the elimination of > 95% of germline sequences, which priorly adopt heterochromatin structure via H3K27me3. Simultaneously, 27nt-ncRNAs become synthesized from parental transcripts and are bound by the Argonaute protein PIWI1. RESULTS: These 27nt-ncRNAs cover sequences destined to the developing macronucleus and are thought to protect them from degradation...
June 12, 2018: Epigenetics & Chromatin
Tom G Richardson, Philip C Haycock, Jie Zheng, Nicholas J Timpson, Tom R Gaunt, George Davey Smith, Caroline L Relton, Gibran Hemani
We have undertaken a systematic Mendelian randomization (MR) study using methylation quantitative trait loci (meQTL) as genetic instruments to assess the relationship between genetic variation, DNA methylation and 139 complex traits. Using two-sample MR, we identified 1,148 associations across 61 traits where genetic variants were associated with both proximal DNA methylation (i.e. cis-meQTL) and complex trait variation (P < 1.39x10-08). Joint likelihood mapping provided evidence that the genetic variant which influenced DNA methylation levels for 348 of these associations across 47 traits was also responsible for variation in complex traits...
June 8, 2018: Human Molecular Genetics
Santiago Haase, María Belén Garcia-Fabiani, Stephen Carney, David Altshuler, Felipe J Núñez, Flor M Méndez, Fernando Núñez, Pedro R Lowenstein, Maria G Castro
ATRX is a chromatin remodeling protein whose main function is the deposition of the histone variant H3.3. ATRX mutations are widely distributed in glioma, and correlate with alternative lengthening of telomeres (ALT) development, but they also affect other cellular functions related to epigenetic regulation. Areas covered: We discuss the main molecular characteristics of ATRX, from its various functions in normal development to the effects of its loss in ATRX syndrome patients and animal models. We focus on the salient consequences of ATRX mutations in cancer, from a clinical to a molecular point of view, focusing on both adult and pediatric glioma...
June 11, 2018: Expert Opinion on Therapeutic Targets
Sarah Kerns, Kuang-Hsiang Chuang, William Hall, Zachary Werner, Yuhchyau Chen, Harry Ostrer, Catharine West, Barry Rosenstein
Radiobiology research is building the foundation for applying genomics in precision radiation oncology. Advances in high-throughput approaches will underpin increased understanding of radiosensitivity and the development of future predictive assays for clinical application. There is an established contribution of genetics as a risk factor for radiotherapy side-effects. An individual's radiosensitivity is an inherited polygenic trait with an architecture that includes rare mutations in a few genes that confer large effects and common variants in many genes with small effects...
June 11, 2018: British Journal of Radiology
Jin Kang, Yea Woon Kim, AeRi Kim
Histone variants H3.3 and H2A.Z are often enriched in enhancers and transcriptionally active genes. However, the incorporation dynamics of these variants and the mechanisms of their incorporation are unclear. Here, we examined the distribution of H3.3 and H2A.Z in the human β-globin locus and analyzed their incorporation dynamics during transcription activation. Locus control region hypersensitive sites (LCR HSs), acting as enhancers, and active globin genes were enriched by H3.3 and H2A.Z in erythroid K562 cells, but inactive globin genes were not...
June 4, 2018: Biochimica et Biophysica Acta
Sarah Elizabeth Jones, Lars Olsen, Jerzy Dorosz, Signe Teuber Seger, Jan Legaard Andersson, Line Hyltoft Kristensen, Michael Gajhede
The KDM6 subfamily of histone lysine demethylases has recently been implicated as a putative target in treatment of a number of diseases, making the availability of potent and selective inhibitors important. Due to high sequence similarity of the catalytic domain of Jumonji C histone demethylases, development of small molecule family specific inhibitors has, however, proven challenging. One approach to achieve selective inhibition of these enzymes is the use of peptides derived from the substrate the histone H3 C-terminus...
June 7, 2018: Chembiochem: a European Journal of Chemical Biology
Andrea Giberson, Bratati Saha, Kalisa Campbell, Carin Christou, Kathy L Poulin, Robin J Parks
Adenovirus (Ad) DNA undergoes dynamic changes in protein association as the virus progresses through its replicative cycle. Within the virion, the Ad DNA associates primarily with the virus-encoded, protamine-like protein VII. During the early phase of infection (~6 h), the viral DNA showed declining association with VII, suggesting that VII was removed from at least some regions of the viral DNA. Within 6 h, the viral DNA was wrapped into a repeating nucleosome-like array containing the histone variant H3...
June 6, 2018: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
Fang Yao, Peng Yu, Yue Li, Xinli Yuan, Zheng Li, Tao Zhang, Fei Liu, Yingbao Wang, Yin Wang, Dandan Li, Baihui Ma, Chang Shu, Wei Kong, Bingying Zhou, Li Wang
Background -Histone variants endow chromatin with specific structures, and play essential roles in development and diseases. However, little is known about their roles in controlling cell identity in vascular diseases. Methods -Given the cell heterogeneity in atherosclerotic lesions, we applied single-cell RNA-Seq to analyze diseased human arteries, and identified histone variant H2A.Z as a key histone signature to maintain vascular smooth muscle cell (VSMC) identity. Results -We show that H2A.Z occupies genomic regions near VSMC marker genes and its occupancy is decreased in VSMCs undergoing dedifferentiation...
June 5, 2018: Circulation
Andrzej Kowalski, Janusz Markowski
From the liver tissues of brown hare individuals that lived in two various habitats, i.e., the agricultural region with the predominant farms and the industrial area near a metallurgical plant, histones H1 were analyzed to compare their within and between population variability. Furthermore, because agricultural production emits mainly organic pollutants and metallurgical industry is a primarily source of inorganic contaminations, we wanted to check how the brown hare individuals are sensitive for both agents...
June 5, 2018: Archives of Environmental Contamination and Toxicology
Yunyun Jin, Qing Yang, Jiayang Gao, Qi Tang, Bo Duan, Ting Yu, Xinglei Qi, Jiming Liu, Rongmin Wang, Ruihua Dang, Chuzhao Lei, Hong Chen, Xianyong Lan
Growth traits are complex quantitative traits controlled by numerous candidate genes, and they can be well-evaluated using body measurement traits. As the members of the nicotinamide adenine dinucleotide-dependent family of histone deacetylases, class I sirtuin genes (including SIRT1, SIRT2 and SIRT3) play crucial roles in regulating lipid metabolism, cellular growth and metabolism, suggesting that they are potential candidate genes affecting body measurement traits in animals. Hence, the objective of this work aimed to detect novel insertions/deletions (indels) of SIRT1, SIRT2 and SIRT3 genes in 955 cattle belonging to five breeds, as well as to evaluate their effects on body measurement traits...
June 4, 2018: Biochemical Genetics
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