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histone modification chromatin

Kumaran Nagalingam, Michał T Lorenc, Sahana Manoli, Stephen L Cameron, Anthony R Clarke, Kevin J Dudley
Interactions between DNA and proteins located in the cell nucleus play an important role in controlling physiological processes by specifying, augmenting and regulating context-specific transcription events. Chromatin immunoprecipitation (ChIP) is a widely used methodology to study DNA-protein interactions and has been successfully used in various cell types for over three decades. More recently, by combining ChIP with genomic screening technologies and Next Generation Sequencing (e.g. ChIP-seq), it has become possible to profile DNA-protein interactions (including covalent histone modifications) across entire genomes...
2018: PloS One
Sun-Ju Yi, Kyunghwan Kim
Chromatin is an intelligent building block that can express either external or internal needs through structural changes. To date, three methods to change chromatin structure and regulate gene expression have been well-documented: histone modification, histone exchange, and ATP-dependent chromatin remodeling. Recently, a growing body of literature has suggested that histone tail cleavage is related to various cellular processes including stem cell differentiation, osteoclast differentiation, granulocyte differentiation, mammary gland differentiation, viral infection, aging, and yeast sporulation...
March 15, 2018: BMB Reports
Emily C Sheppard, Rikke Brandstrup Morrish, Michael J Dillon, Rebecca Leyland, Richard Chahwan
Epigenetic modifications, such as histone modifications, DNA methylation status, and non-coding RNAs (ncRNA), all contribute to antibody maturation during somatic hypermutation (SHM) and class-switch recombination (CSR). Histone modifications alter the chromatin landscape and, together with DNA primary and tertiary structures, they help recruit Activation-Induced Cytidine Deaminase (AID) to the immunoglobulin (Ig) locus. AID is a potent DNA mutator, which catalyzes cytosine-to-uracil deamination on single-stranded DNA to create U:G mismatches...
2018: Frontiers in Immunology
Philippa Melamed, Majd Haj, Yahav Yosefzon, Sergei Rudnizky, Andrea Wijeweera, Lilach Pnueli, Ariel Kaplan
Gonadotropin-releasing hormone (GnRH) stimulates the expression of multiple genes in the pituitary gonadotropes, most notably to induce synthesis of the gonadotropins, luteinizing hormone (LH), and follicle-stimulating hormone (FSH), but also to ensure the appropriate functioning of these cells at the center of the mammalian reproductive endocrine axis. Aside from the activation of gene-specific transcription factors, GnRH stimulates through its membrane-bound receptor, alterations in the chromatin that facilitate transcription of its target genes...
2018: Frontiers in Endocrinology
Kyle T Householder, Danielle M DiPerna, Eugene P Chung, Anne Rosa Luning, Duong T Nguyen, Sarah E Stabenfeldt, Shwetal Mehta, Rachael W Sirianni
Histone deacetylases (HDACs) are known to be key enzymes in cancer development and progression through their modulation of chromatin structure and the expression and post-translational modification of numerous proteins. Aggressive dedifferentiated tumors, like glioblastoma, frequently overexpress HDACs, while HDAC inhibition can lead to cell cycle arrest, promote cellular differentiation and induce apoptosis. Although multiple HDAC inhibitors, such as quisinostat, are of interest in oncology due to their potent in vitro efficacy, their failure in the clinic as monotherapies against solid tumors has been attributed to poor delivery...
February 24, 2018: Colloids and Surfaces. B, Biointerfaces
Matteo Vecellio, Adrian Cortes, Amity R Roberts, Jonathan Ellis, Carla Jayne Cohen, Julian C Knight, Matthew A Brown, Paul Bowness, Bryan Paul Wordsworth
Objectives: To explore the functions of RUNX3 single nucleotide polymorphisms (SNPs) associated with ankylosing spondylitis (AS). Methods: Individual SNP associations were evaluated in 4230 UK cases. Their effects on transcription factor (TF) binding, transcription regulation, chromatin modifications, gene expression and gene interactions were tested by database interrogation, luciferase reporter assays, electrophoretic mobility gel shifts, chromatin immunoprecipitation and real-time PCR...
2018: RMD Open
Charles J Underwood, Kyuha Choi, Christophe Lambing, Xiaohui Zhao, Heïdi Serra, Filipe Borges, Joe Simorowski, Evan Ernst, Yannick Jacob, Ian R Henderson, Robert A Martienssen
Eukaryotic centromeres contain the kinetochore, which connects chromosomes to the spindle allowing segregation. During meiosis, centromeres are suppressed for inter-homolog crossover, as recombination in these regions can cause chromosome missegregation and aneuploidy. Plant centromeres are surrounded by transposon-dense pericentromeric heterochromatin that is epigenetically silenced by histone 3 lysine 9 dimethylation (H3K9me2), and DNA methylation in CG and non-CG sequence contexts. However, the role of these chromatin modifications in control of meiotic recombination in the pericentromeres is not fully understood...
March 12, 2018: Genome Research
Marta Fontcuberta-PiSunyer, Sara Cervantes, Eulàlia Miquel, Sergio Mora-Castilla, Louise C Laurent, Angel Raya, Ramon Gomis, Rosa Gasa
Posttranscriptional modifications of histones constitute an epigenetic mechanism that is closely linked to both gene silencing and activation events. Trimethylation of Histone3 at lysine 27 (H3K27me3) is a repressive mark that associates with developmental gene regulation during differentiation programs. In the developing pancreas, expression of the transcription factor Neurogenin3 in multipotent progenitors initiates endocrine differentiation that culminates in the generation of all pancreatic islet cell lineages, including insulin-producing beta cells...
March 9, 2018: Biochimica et Biophysica Acta
Timothy J Jarome, Rishi K Devulapalli
Cellular models of memory formation have focused on the need for protein synthesis. Recently, evidence has emerged that protein degradation mediated by the ubiquitin-proteasome system (UPS) is also important for this process. This has led to revised cellular models of memory formation that focus on a balance between protein degradation and synthesis. However, protein degradation is only one function of the UPS. Studies using single-celled organisms have shown that non-proteolytic ubiquitin-proteasome signaling is involved in histone modifications and DNA methylation, suggesting that ubiquitin and the proteasome can regulate chromatin remodeling independent of protein degradation...
March 1, 2018: Neuroscientist: a Review Journal Bringing Neurobiology, Neurology and Psychiatry
Ryuichiro Nakato, Katsuhiko Shirahige
Motivation: Chromatin immunoprecipitation followed by sequencing (ChIP-seq) can detect read-enriched DNA loci for point-source (e.g., transcription factor binding) and broad-source factors (e.g., various histone modifications). Although numerous quality metrics for ChIP-seq data have been developed, the 'peaks' thus obtained are still difficult to assess with respect to signal-to-noise ratio (S/N) and the percentage of false positives. Results: We developed a quality-assessment tool for ChIP-seq data, SSP (strand-shift profile), that quantifies S/N and peak reliability without peak calling...
March 8, 2018: Bioinformatics
Melda Onal, Alex H Carlson, Jeff D Thostenson, Nancy A Benkusky, Mark B Meyer, Seong M Lee, J Wesley Pike
Fibroblast growth factor 23 (FGF23) production is regulated by both calciotropic hormones and inflammation. Consistent with this, elevated FGF23 levels are associated with inflammatory markers as well as parathyroid hormone (PTH) in various disease states, including chronic kidney disease (CKD). However, the molecular mechanisms underpinning Fgf23 transcription in response to these regulators are largely unknown. We therefore utilized chromatin immunoprecipitation followed by DNA sequencing (ChIP-seq) data from an osteocyte cell line to identify potential regulatory regions of the Fgf23 gene...
January 2018: JBMR Plus
Linbo Gao, David Cheng, Jie Yang, Renyi Wu, Wenji Li, Ah-Ng Kong
Increasing evidence suggests that epigenetic aberrations contribute to the development and progression of cancers such as lung cancer. The promoter region of miR-9-3 was recently found to be hypermethylated in lung cancer, resulting in down-regulation of miR-9-3 and poor patient prognosis. Sulforaphane (SFN), a natural compound that is obtained from cruciferous vegetables, has potent anticancer activities. In this study, we aimed to investigate the effect of SFN on restoring the miR-9-3 level in lung cancer A549 cells through epigenetic regulation...
February 9, 2018: Journal of Nutritional Biochemistry
Darren K Patten, Giacomo Corleone, Luca Magnani
Chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq) has become an essential tool for epigenetic scientists. ChIP-seq is used to map protein-DNA interactions and epigenetic marks such as histone modifications at the genome-wide level. Here we describe a complete ChIP-seq laboratory protocol (tailored toward processing tissue samples as well as cell lines) and the bioinformatic pipelines utilized for handling raw sequencing files through to peak calling.
2018: Methods in Molecular Biology
Jessica B Lee, Albert J Keung
Chromatin immunoprecipitation (ChIP) is an invaluable method to characterize interactions between proteins and genomic DNA, such as the genomic localization of transcription factors and posttranslational modification of histones. DNA and proteins are reversibly and covalently crosslinked using formaldehyde. Then the cells are lysed to release the chromatin. The chromatin is fragmented into smaller sizes either by micrococcal nuclease (MNase) or sonication and then purified from other cellular components. The protein-DNA complexes are enriched by immunoprecipitation (IP) with antibodies that target the epitope of interest...
2018: Methods in Molecular Biology
Srikanth Appikonda, Kaushik N Thakkar, Parantu K Shah, Sharon Y R Dent, Jannik N Andersen, Michelle Craig Barton
Proteins with domains that recognize and bind post-translational modifications (PTMs) of histones are collectively termed epigenetic readers. Numerous interactions between specific reader protein domains and histone PTMs and their regulatory outcomes have been reported, but little is known about how reader proteins may in turn be modulated by these interactions. Tripartite motif-containing protein 24 (TRIM24) is a histone reader aberrantly expressed in multiple cancers. Here, our investigation revealed functional crosstalk between histone acetylation and TRIM24 SUMOylation...
March 9, 2018: Journal of Biological Chemistry
Christian L Lino Cardenas, Chase W Kessinger, Yisha Cheng, Carolyn MacDonald, Thomas MacGillivray, Brian Ghoshhajra, Luai Huleihel, Saifar Nuri, Ashish S Yeri, Farouc A Jaffer, Naftali Kaminski, Patrick Ellinor, Neal L Weintraub, Rajeev Malhotra, Eric M Isselbacher, Mark E Lindsay
Thoracic aortic aneurysm (TAA) has been associated with mutations affecting members of the TGF-β signaling pathway, or components and regulators of the vascular smooth muscle cell (VSMC) actomyosin cytoskeleton. Although both clinical groups present similar phenotypes, the existence of potential common mechanisms of pathogenesis remain obscure. Here we show that mutations affecting TGF-β signaling and VSMC cytoskeleton both lead to the formation of a ternary complex comprising the histone deacetylase HDAC9, the chromatin-remodeling enzyme BRG1, and the long noncoding RNA MALAT1...
March 8, 2018: Nature Communications
Dalibor Miklík, Filip Šenigl, Jiří Hejnar
Individual groups of retroviruses and retroviral vectors differ in their integration site preference and interaction with the host genome. Hence, immediately after infection genome-wide distribution of integrated proviruses is non-random. During long-term in vitro or persistent in vivo infection, the genomic position and chromatin environment of the provirus affects its transcriptional activity. Thus, a selection of long-term stably expressed proviruses and elimination of proviruses, which have been gradually silenced by epigenetic mechanisms, helps in the identification of genomic compartments permissive for proviral transcription...
March 8, 2018: Viruses
Marcia Manterola, Taylor M Brown, Min Young Oh, Corey Garyn, Bryan J Gonzalez, Debra J Wolgemuth
The double bromodomain and extra-terminal domain (BET) proteins are critical epigenetic readers that bind to acetylated histones in chromatin and regulate transcriptional activity and modulate changes in chromatin structure and organization. The testis-specific BET member, BRDT, is essential for the normal progression of spermatogenesis as mutations in the Brdt gene result in complete male sterility. Although BRDT is expressed in both spermatocytes and spermatids, loss of the first bromodomain of BRDT leads to severe defects in spermiogenesis without overtly compromising meiosis...
March 2018: PLoS Genetics
Johayra Simithy, Simone Sidoli, Benjamin A Garcia
The chromatin fiber is the control panel of eukaryotic cells. Chromatin is mostly composed of DNA, which contains the genetic instruction for cell phenotype, and histone proteins, which provide the scaffold for chromatin folding and part of the epigenetic inheritance. Histone writers/erasers "flag" chromatin regions by catalyzing/removing covalent histone post-translational modifications (PTMs). Histone PTMs chemically contribute to chromatin relaxation or compaction and recruit histone readers to modulate DNA readout...
March 7, 2018: Proteomics
Sun-Ju Yi, Seong Yun Hwang, Myung-Ju Oh, Yang-Hoon Kim, Hojin Ryu, Sung-Keun Rhee, Byung H Jhun, Kyunghwan Kim
Signal transduction pathways regulate the gene expression by altering chromatin dynamics in response to mitogens. Ras proteins are key regulators linking extracellular stimuli to a diverse range of biological responses associated with gene regulation. In mammals, the three ras genes encode four Ras protein isoforms: H-Ras, K-Ras4A, K-Ras4B, and N-Ras. Although emerging evidence suggests that Ras isoforms differentially regulate gene expressions and are functionally nonredundant, the mechanisms underlying Ras specificity and Ras signaling effects on gene expression remain unclear...
2018: BioMed Research International
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