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https://www.readbyqxmd.com/read/28644763/methyltransferase-g9a-regulates-osteogenesis-via-twist-gene-repression
#1
N Higashihori, B Lehnertz, A Sampaio, T M Underhill, F Rossi, J M Richman
Here we investigate the role of epigenetic factors in controlling the timing of cranial neural crest cell differentiation. The gene coding for histone H3 lysine 9 methyltransferase G9A was conditionally deleted in neural crest cells with Wnt1-Cre. The majority of homozygous-null animals survived to birth but thereafter failed to thrive. Phenotypic analysis of postnatal animals revealed that the mutants displayed incomplete ossification and 20% shorter jaws as compared to their wild-type littermates. At E13...
June 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28644004/the-intricate-effects-of-alpha-amino-and-lysine-modifications-on-arginine-methylation-on-the-n-terminal-tail-of-histone-h4
#2
Melody D Fulton, Jing Zhang, Maomao He, Meng-Chiao Ho, Y George Zheng
Chemical modifications on the DNA and nucleosomal histones tightly control the gene transcription program in eukaryotic cells. The "histone code" hypothesis proposes that the frequency, combination, and location of post-translational modifications (PTMs) on the core histones compose a complex network of epigenetic regulation. Currently, there are at least 23 different types and over 450 histone PTMs discovered, and the PTMs on lysine and arginine residues account for a crucial part of the histone code. Although significant progress has been achieved in recent years, the molecular basis for the histone code is far from being fully understood...
June 23, 2017: Biochemistry
https://www.readbyqxmd.com/read/28630499/spatio-temporal-analysis-of-coding-and-long-noncoding-transcripts-during-maize-endosperm-development
#3
Eun-Deok Kim, Yuqing Xiong, Youngjae Pyo, Dong-Hwan Kim, Byung-Ho Kang, Sibum Sung
The maize endosperm consists of three major compartmentalized cell types: the starchy endosperm (SE), the basal endosperm transfer cell layer (BETL), and the aleurone cell layer (AL). Differential genetic programs are activated in each cell type to construct functionally and structurally distinct cells. To compare gene expression patterns involved in maize endosperm cell differentiation, we isolated transcripts from cryo-dissected endosperm specimens enriched with BETL, AL, or SE at 8, 12, and 16 days after pollination (DAP)...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28623160/basic-concepts-in-molecular-biology-related-to-genetics-and-epigenetics
#4
Dolores Corella, Jose M Ordovas
The observation that "one size does not fit all" for the prevention and treatment of cardiovascular disease, among other diseases, has driven the concept of precision medicine. The goal of precision medicine is to provide the best-targeted interventions tailored to an individual's genome. The human genome is composed of billions of sequence arrangements containing a code that controls how genes are expressed. This code depends on other nonstatic regulators that surround the DNA and constitute the epigenome...
June 13, 2017: Revista Española de Cardiología
https://www.readbyqxmd.com/read/28612427/simulation-based-investigation-of-deleterious-nssnp-s-in-atxn2-gene-and-its-structural-consequence-towards-spinocerebellar-ataxia
#5
Siddharth Sinha, Sharad Verma, Aditi Singh, Pallavi Somvanshi, Abhinav Grover
Spinocerebellar degeneration, termed as ataxia is a neurological disorder of central nervous system, characterized by limb in-coordination and a progressive gait. The patient also demonstrates specific symptoms of muscle weakness, slurring of speech, and decreased vibration senses. Expansion of polyglutamine trinucleotide (CAG) within ATXN2 gene with 35 or more repeats, results in spinocerebellar ataxia type-2. Protein ataxin-2 coded by ATXN2 gene has been reported to have a crucial role in translation of the genetic information through sequestering the histone acetyl transferases (HAT) resulting in a state of hypo-acetylation...
June 14, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28604753/let-7b-and-let-7c-micrornas-promote-histone-h2b-ubiquitylation-and-inhibit-cell-migration-by-targeting-multiple-components-of-the-h2b-deubiquitylation-machinery
#6
A Spolverini, G Fuchs, D R Bublik, M Oren
Monoubiquitylation of histone H2B (H2Bub1) is catalyzed mainly by the RNF20/RNF40 complex and erased by multiple deubiquitylating enzymes (DUBs). H2Bub1 influences many aspects of chromatin function, including transcription regulation and DNA repair. Cancer cells often display reduced levels of H2Bub1, and this reduction may contribute to cancer progression. The let-7 family of microRNAs (miRNAs) comprises multiple members with reported tumor-suppressive features, whose expression is frequently downregulated in cancer...
June 12, 2017: Oncogene
https://www.readbyqxmd.com/read/28604729/dnmt-and-hdac-inhibitors-induce-cryptic-transcription-start-sites-encoded-in-long-terminal-repeats
#7
David Brocks, Christopher R Schmidt, Michael Daskalakis, Hyo Sik Jang, Nakul M Shah, Daofeng Li, Jing Li, Bo Zhang, Yiran Hou, Sara Laudato, Daniel B Lipka, Johanna Schott, Holger Bierhoff, Yassen Assenov, Monika Helf, Alzbeta Ressnerova, Md Saiful Islam, Anders M Lindroth, Simon Haas, Marieke Essers, Charles D Imbusch, Benedikt Brors, Ina Oehme, Olaf Witt, Michael Lübbert, Jan-Philipp Mallm, Karsten Rippe, Rainer Will, Dieter Weichenhan, Georg Stoecklin, Clarissa Gerhäuser, Christopher C Oakes, Ting Wang, Christoph Plass
Several mechanisms of action have been proposed for DNA methyltransferase and histone deacetylase inhibitors (DNMTi and HDACi), primarily based on candidate-gene approaches. However, less is known about their genome-wide transcriptional and epigenomic consequences. By mapping global transcription start site (TSS) and chromatin dynamics, we observed the cryptic transcription of thousands of treatment-induced non-annotated TSSs (TINATs) following DNMTi and HDACi treatment. The resulting transcripts frequently splice into protein-coding exons and encode truncated or chimeric ORFs translated into products with predicted abnormal or immunogenic functions...
June 12, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28598385/the-roles-of-long-non-protein-coding-rnas-in-osteo-adipogenic-lineage-commitment
#8
REVIEW
Hirotaka Yoshioka, Yuji Yoshiko
Osteoblasts and adipocytes share a common mesenchymal progenitor in the bone marrow. This implies that a reciprocal relationship exists between osteogenic and adipogenic differentiation. Further, cells of osteoblast lineage transdifferentiate into adipocytes under some circumstances. Dysregulation of osteo-adipogenic fate-determination leads to bone diseases such as osteoporosis, accompanied by an increase in bone marrow adipose tissue. Thus, the fine-tuning of osteo-adipogenesis is necessary for bone homeostasis...
June 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28597910/a-complete-association-of-an-intronic-snp-rs6798742-with-origin-of-spinocerebellar-ataxia-type-7-cag-expansion-loci-in-the-indian-and-mexican-population
#9
Mohammed Faruq, Jonathan J Magaña, Varun Suroliya, Ankita Narang, Nadia M Murillo-Melo, Oscar Hernández-Hernández, Achal K Srivastava, Mitali Mukerji
Spinocerebellar ataxia type 7 (SCA7) is a rare neurogenetic disorder caused by highly unstable CAG repeat expansion mutation in coding region of SCA7. We aimed to understand the effect of diverse ATXN7 cis-element in correlation with CAG expansion mutation of SCA7. We initially performed an analysis to identify the haplotype background of CAG expanded alleles using eight bi-allelic single nucleotide polymorphisms (SNPs) flanking an ATXN7-CAG expansion in 32 individuals from nine unrelated Indian SCA7 families and 88 healthy controls...
June 9, 2017: Annals of Human Genetics
https://www.readbyqxmd.com/read/28587163/a-tox21-approach-to-altered-epigenetic-landscapes-assessing-epigenetic-toxicity-pathways-leading-to-altered-gene-expression-and-oncogenic-transformation-in-vitro
#10
REVIEW
Craig L Parfett, Daniel Desaulniers
An emerging vision for toxicity testing in the 21st century foresees in vitro assays assuming the leading role in testing for chemical hazards, including testing for carcinogenicity. Toxicity will be determined by monitoring key steps in functionally validated molecular pathways, using tests designed to reveal chemically-induced perturbations that lead to adverse phenotypic endpoints in cultured human cells. Risk assessments would subsequently be derived from the causal in vitro endpoints and concentration vs...
June 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28587112/is-there-a-role-for-genomics-in-the-management-of-hypertension
#11
REVIEW
Jacopo Burrello, Silvia Monticone, Fabrizio Buffolo, Martina Tetti, Franco Veglio, Tracy A Williams, Paolo Mulatero
Hypertension (HTN) affects about 1 billion people worldwide and the lack of a single identifiable cause complicates its treatment. Blood pressure (BP) levels are influenced by environmental factors, but there is a strong genetic component. Linkage analysis has identified several genes involved in Mendelian forms of HTN and the associated pathophysiological mechanisms have been unravelled, leading to targeted therapies. The majority of these syndromes are due to gain-of-function or loss-of-functions mutations, resulting in an alteration of mineralocorticoid, glucocorticoid, or sympathetic pathways...
May 26, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28583068/lncrna-screen-an-interactive-platform-for-computationally-screening-long-non-coding-rnas-in-large-genomics-datasets
#12
Yixiao Gong, Hsuan-Ting Huang, Yu Liang, Thomas Trimarchi, Iannis Aifantis, Aristotelis Tsirigos
BACKGROUND: Long non-coding RNAs (lncRNAs) have emerged as a class of factors that are important for regulating development and cancer. Computational prediction of lncRNAs from ultra-deep RNA sequencing has been successful in identifying candidate lncRNAs. However, the complexity of handling and integrating different types of genomics data poses significant challenges to experimental laboratories that lack extensive genomics expertise. RESULT: To address this issue, we have developed lncRNA-screen, a comprehensive pipeline for computationally screening putative lncRNA transcripts over large multimodal datasets...
June 5, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28582573/integrative-analysis-of-multiple-genomic-variables-using-a-hierarchical-bayesian-model
#13
Martin Schäfer, Hans-Ulrich Klein, Holger Schwender
Motivation: Genes showing congruent differences in several genomic variables between two biological conditions are crucial to unravel causalities behind phenotypes of interest. Detecting such genes is important in biomedical research, e.g. when identifying genes responsible for cancer development. Small sample sizes common in next-generation sequencing studies are a key challenge, and there are still only very few statistical methods to analyze more than two genomic variables in an integrative, model-based way...
June 5, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28573430/critical-effects-of-epigenetic-regulation-in-pulmonary-arterial-hypertension
#14
REVIEW
Dewei Chen, Wenxiang Gao, Shouxian Wang, Bing Ni, Yuqi Gao
Pulmonary arterial hypertension (PAH) is characterized by persistent pulmonary vasoconstriction and pulmonary vascular remodeling. The pathogenic mechanisms of PAH remain to be fully clarified and measures of effective prevention are lacking. Recent studies; however, have indicated that epigenetic processes may exert pivotal influences on PAH pathogenesis. In this review, we summarize the latest research findings regarding epigenetic regulation in PAH, focusing on the roles of non-coding RNAs, histone modifications, ATP-dependent chromatin remodeling and DNA methylation, and discuss the potential of epigenetic-based therapies for PAH...
June 1, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28572580/uropa-a-tool-for-universal-robust-peak-annotation
#15
Maria Kondili, Annika Fust, Jens Preussner, Carsten Kuenne, Thomas Braun, Mario Looso
The annotation of genomic ranges of interest represents a recurring task for bioinformatics analyses. These ranges can originate from various sources, including peaks called for transcription factor binding sites (TFBS) or histone modification ChIP-seq experiments, chromatin structure and accessibility experiments (such as ATAC-seq), but also from other types of predictions that result in genomic ranges. While peak annotation primarily driven by ChiP-seq was extensively explored, many approaches remain simplistic ("most closely located TSS"), rely on fixed pre-built references, or require complex scripting tasks on behalf of the user...
June 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28572116/kdm5a-demethylase-erasing-histone-modifications-to-promote-repair-of-dna-breaks
#16
Brendan D Price
Repairing DNA breaks within the complexity of the cell chromatin is challenging. In this issue, Gong et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201611135) identify the histone demethylase KDM5A as a critical editor of the cells' "histone code" that is required to recruit DNA repair complexes to DNA breaks.
June 1, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28566502/inhibition-of-hdac-enhances-stat-acetylation-blocks-nf-%C3%AE-b-and-suppresses-the-renal-inflammation-and-fibrosis-in-npr1-haplotype-male-mice
#17
Prerna Kumar, Venkateswara R Gogulamudi, Ramu Peryasamy, Giri Raghavaraju, Umadevi Subramania, Kailash N Pandey
Guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) plays a critical role in the regulation of blood pressure and fluid volume homeostasis. Mice lacking functional Npr1 (coding for GC-A/NPRA) exhibit hypertension and congestive heart failure. However, the underlying mechanisms remain largely less clear. The objective of the present study was to determine the physiological efficacy and impact of all-trans retinoic acid (ATRA) and sodium butyrate (NaBu) in ameliorating the renal fibrosis, inflammation, and hypertension in Npr1 gene-disrupted haplotype (1-copy; +/-) mice (50% expression levels of NPRA)...
May 31, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28561778/ezh2-in-cancer-progression-and-potential-application-in-cancer-therapy-a-friend-or-foe
#18
REVIEW
Ke-Sin Yan, Chia-Yuan Lin, Tan-Wei Liao, Cheng-Ming Peng, Shou-Chun Lee, Yi-Jui Liu, Wing P Chan, Ruey-Hwang Chou
Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase, catalyzes tri-methylation of histone H3 at Lys 27 (H3K27me3) to regulate gene expression through epigenetic machinery. EZH2 functions as a double-facet molecule in regulation of gene expression via repression or activation mechanisms, depending on the different cellular contexts. EZH2 interacts with both histone and non-histone proteins to modulate diverse physiological functions including cancer progression and malignancy. In this review article, we focused on the updated information regarding microRNAs (miRNAs) and long non coding RNAs (lncRNAs) in regulation of EZH2, the oncogenic and tumor suppressive roles of EZH2 in cancer progression and malignancy, as well as current pre-clinical and clinical trials of EZH2 inhibitors...
May 31, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28555639/clonally-stable-v%C3%AE%C2%BA-allelic-choice-instructs-ig%C3%AE%C2%BA-repertoire
#19
Rena Levin-Klein, Shira Fraenkel, Michal Lichtenstein, Louise S Matheson, Osnat Bartok, Yuval Nevo, Sebastian Kadener, Anne E Corcoran, Howard Cedar, Yehudit Bergman
Although much has been done to understand how rearrangement of the Igκ locus is regulated during B-cell development, little is known about the way the variable (V) segments themselves are selected. Here we show, using B6/Cast hybrid pre-B-cell clones, that a limited number of V segments on each allele is stochastically activated as characterized by the appearance of non-coding RNA and histone modifications. The activation states are clonally distinct, stable across cell division and developmentally important in directing the Ig repertoire upon differentiation...
May 30, 2017: Nature Communications
https://www.readbyqxmd.com/read/28546713/current-concepts-of-epigenetics-in-testicular-cancer
#20
REVIEW
Alfredo Harb-De la Rosa, Meenakkshy Manoharan, Ahmed Saeed Goolam
Testicular germ cell tumors (GCTs) are characterized into seminomas (SGCTs) and non-seminomatous testicular germ cell tumors (NSGCTs). Serum tumor markers (STMs) play an important role in testicular cancer as they provide useful information for diagnosis, staging, and detection of recurrence. Nonetheless, additional tumor markers for early diagnosis and therapeutic options are required to enhance specificity of serological diagnosis of testes cancers. Epigenetics is defined as inherited changes in gene expression that are not encoded in the DNA structure...
June 2017: Indian Journal of Surgical Oncology
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