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https://www.readbyqxmd.com/read/28820292/p53-binding-sites-in-normal-and-cancer-cells-are-characterized-by-distinct-chromatin-context
#1
Feifei Bao, Peter R LoVerso, Jeffrey N Fisk, Victor B Zhurkin, Feng Cui
The tumor suppressor protein p53 interacts with DNA in a sequence-dependent manner. Thousands of p53 binding sites have been mapped genome-wide in normal and cancer cells. However, the way p53 selectively binds its cognate sites in different types of cells is not fully understood. Here, we performed a comprehensive analysis of 25 published p53 cistromes and identified 3,551 and 6,039 'high-confidence' binding sites in normal and cancer cells, respectively. Our analysis revealed two distinct epigenetic features underlying p53-DNA interactions in vivo...
August 18, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28819152/dissecting-the-genomic-activity-of-a-transcriptional-regulator-by-the-integrative-analysis-of-omics-data
#2
Giulio Ferrero, Valentina Miano, Marco Beccuti, Gianfranco Balbo, Michele De Bortoli, Francesca Cordero
In the study of genomic regulation, strategies to integrate the data produced by Next Generation Sequencing (NGS)-based technologies in a meaningful ensemble are eagerly awaited and must continuously evolve. Here, we describe an integrative strategy for the analysis of data generated by chromatin immunoprecipitation followed by NGS which combines algorithms for data overlap, normalization and epigenetic state analysis. The performance of our strategy is illustrated by presenting the analysis of data relative to the transcriptional regulator Estrogen Receptor alpha (ERα) in MCF-7 breast cancer cells and of Glucocorticoid Receptor (GR) in A549 lung cancer cells...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819009/the-aaa-atpase-p97-a-cellular-multitool
#3
REVIEW
Lasse Stach, Paul S Freemont
The AAA+ (ATPases associated with diverse cellular activities) ATPase p97 is essential to a wide range of cellular functions, including endoplasmic reticulum-associated degradation, membrane fusion, NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) activation and chromatin-associated processes, which are regulated by ubiquitination. p97 acts downstream from ubiquitin signaling events and utilizes the energy from ATP hydrolysis to extract its substrate proteins from cellular structures or multiprotein complexes...
August 17, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28816576/a-demethylation-deficient-isoform-of-the-lysine-demethylase-kdm2a-interacts-with-pericentromeric-heterochromatin-in-an-hp1a-dependent-manner
#4
Dijana Lađinović, Jitka Novotná, Soňa Jakšová, Ivan Raška, Tomáš Vacík
Histone modifications have a profound impact on the chromatin structure and gene expression and their correct establishment and recognition is essential for correct cell functioning. Malfunction of histone modifying proteins is associated with developmental defects and diseases and detailed characterization of these proteins is therefore very important. The lysine specific demethylase KDM2A is a CpG island binding protein that has been studied predominantly for its ability to regulate CpG island-associated gene promoters by demethylating their H3K36me2...
August 17, 2017: Nucleus
https://www.readbyqxmd.com/read/28816391/cytoskeleton-and-nucleoskeleton-involvement-in-processes-of-cytomixis-in-plants
#5
REVIEW
E A Kravets, A I Yemets, Ya B Blume
Cytomixis, is a form of cell-to-cell nuclear migration that involves the interaction of dynamic cytoskeletal components with the nucleus through signalling systems and linker complexes. In cytomixis two known mechanisms can be involved: actomyosin and/or microtubules and their associated motors. Perinuclear actin anchors and determines the direction of nuclear movement. In microsporogenesis cytomixis is probably initiated by a cascade of signals that trigger prophase reorganization of nucleus and cytoskeleton, and is a result of cytoskeletal protein activation, as well as a weakening of mechanisms responsible for anchoring the nucleus...
August 17, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28815537/from-heterochromatin-to-long-noncoding-rnas-in-drosophila-expanding-the-arena-of-gene-function-and-regulation
#6
Subhash C Lakhotia
Recent years have witnessed a remarkable interest in exploring the significance of pervasive noncoding transcripts in diverse eukaryotes. Classical cytogenetic studies using the Drosophila model system unraveled the perplexing attributes and "functions" of the "gene"-poor heterochromatin. Recent molecular studies in the fly model are likewise revealing the very diverse and significant roles played by long noncoding RNAs (lncRNAs) in development, gene regulation, chromatin organization, cell and nuclear architecture, etc...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28814964/milk-disrupts-p53-and-dnmt1-the-guardians-of-the-genome-implications-for-acne-vulgaris-and-prostate-cancer
#7
Bodo C Melnik
There is accumulating evidence that milk shapes the postnatal metabolic environment of the newborn infant. Based on translational research, this perspective article provides a novel mechanistic link between milk intake and milk miRNA-regulated gene expression of the transcription factor p53 and DNA methyltransferase 1 (DNMT1), two guardians of the human genome, that control transcriptional activity, cell survival, and apoptosis. Major miRNAs of milk, especially miRNA-125b, directly target TP53 and complex p53-dependent gene regulatory networks...
2017: Nutrition & Metabolism
https://www.readbyqxmd.com/read/28812991/the-retinoblastoma-rb-tumor-suppressor-pushing-back-against-genome-instability-on-multiple-fronts
#8
REVIEW
Renier Vélez-Cruz, David G Johnson
The retinoblastoma (RB) tumor suppressor is known as a master regulator of the cell cycle. RB is mutated or functionally inactivated in the majority of human cancers. This transcriptional regulator exerts its function in cell cycle control through its interaction with the E2F family of transcription factors and with chromatin remodelers and modifiers that contribute to the repression of genes important for cell cycle progression. Over the years, studies have shown that RB participates in multiple processes in addition to cell cycle control...
August 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28810927/stat3-mediated-upregulation-of-lncrna-hoxd-as1-as-a-cerna-facilitates-liver-cancer-metastasis-by-regulating-sox4
#9
Hui Wang, Xisong Huo, Xin-Rong Yang, Jia He, Lijun Cheng, Na Wang, Xuan Deng, Haojie Jin, Ning Wang, Cun Wang, Fangyu Zhao, Jingyuan Fang, Ming Yao, Jia Fan, Wenxin Qin
BACKGROUND: Several of the thousands of human long noncoding RNAs (lncRNAs) have been functionally characterized, yet their potential involvement in hepatocellular carcinoma (HCC) remains poorly understood. METHODS: LncRNA-HOXD-AS1 was identified by microarray and validated by real-time PCR. The clinicopathological significance of HOXD-AS1 was analyzed by Kaplan-Meier method. Chromatin immunoprecipitation was conducted to examine the mechanism of HOXD-AS1 upregulation...
August 14, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28809825/analysis-of-histone-antibody-specificity-with-peptide-microarrays
#10
Evan M Cornett, Bradley M Dickson, Scott B Rothbart
Post-translational modifications (PTMs) on histone proteins are widely studied for their roles in regulating chromatin structure and gene expression. The mass production and distribution of antibodies specific to histone PTMs has greatly facilitated research on these marks. As histone PTM antibodies are key reagents for many chromatin biochemistry applications, rigorous analysis of antibody specificity is necessary for accurate data interpretation and continued progress in the field. This protocol describes an integrated pipeline for the design, fabrication and use of peptide microarrays for profiling the specificity of histone antibodies...
August 1, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28808972/chromosome-conformation-capture-for-research-on-innate-antiviral-immunity
#11
Yoon Jung Kim, Tae Hoon Kim
Chromosome conformation capture (3C) technology has revolutionized our knowledge on chromatin folding and nuclear organization. This cis-loop detection approach can be used to identify candidate regulatory elements interacting with target gene of interest. This chapter introduces the application of 3C technique to investigate a dynamic alteration in the chromosome folding structure or genomic architecture resulting from interaction changes between the enhancer and its target gene. Innate antiviral immunity is one of the well-known gene induction systems, involving rapid first-line response to virus or pathogen to trigger gene expression changes in order to protect cells and to limit further infection...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28806396/inhibiting-myc-binding-to-the-e-box-dna-motif-by-me47-decreases-tumour-xenograft-growth
#12
L C Lustig, D Dingar, W B Tu, C Lourenco, M Kalkat, I Inamoto, R Ponzielli, W C W Chan, J A Shin, L Z Penn
Developing therapeutics to effectively inhibit the MYC oncoprotein would mark a key advance towards cancer patient care as MYC is deregulated in over 50% of human cancers. MYC deregulation is correlated with aggressive disease and poor patient outcome. Despite strong evidence in mouse models that inhibiting MYC would significantly impact tumour cell growth and patient survival, traditional approaches have not yet yielded the urgently needed therapeutic agents that directly target MYC. MYC functions through its interaction with MAX to regulate gene transcription by binding to E-box DNA response elements of MYC target genes...
August 14, 2017: Oncogene
https://www.readbyqxmd.com/read/28804761/unfolding-of-core-nucleosomes-by-parp-1-revealed-by-spfret-microscopy
#13
Daniel C Sultanov, Nadezhda S Gerasimova, Kseniya S Kudryashova, Natalya V Maluchenko, Elena Y Kotova, Marie-France Langelier, John M Pascal, Mikhail P Kirpichnikov, Alexey V Feofanov, Vasily M Studitsky
DNA accessibility to various protein complexes is essential for various processes in the cell and is affected by nucleosome structure and dynamics. Protein factor PARP-1 (poly(ADP-ribose)polymerase 1) increases the accessibility of DNA in chromatin to repair proteins and transcriptional machinery, but the mechanism and extent of this chromatin reorganization are unknown. Here we report on the effects of PARP-1 on single nucleosomes revealed by spFRET (single-particle Förster Resonance Energy Transfer) microscopy...
2017: AIMS Genetics
https://www.readbyqxmd.com/read/28804139/the-interplay-of-epigenetic-marks-during-stem-cell-differentiation-and-development
#14
REVIEW
Yaser Atlasi, Hendrik G Stunnenberg
Chromatin, the template for epigenetic regulation, is a highly dynamic entity that is constantly reshaped during early development and differentiation. Epigenetic modification of chromatin provides the necessary plasticity for cells to respond to environmental and positional cues, and enables the maintenance of acquired information without changing the DNA sequence. The mechanisms involve, among others, chemical modifications of chromatin, changes in chromatin constituents and reconfiguration of chromatin interactions and 3D structure...
August 14, 2017: Nature Reviews. Genetics
https://www.readbyqxmd.com/read/28803781/myc-regulates-chromatin-decompaction-and-nuclear-architecture-during-b-cell-activation
#15
Kyong-Rim Kieffer-Kwon, Keisuke Nimura, Suhas S P Rao, Jianliang Xu, Seolkyoung Jung, Aleksandra Pekowska, Marei Dose, Evan Stevens, Ewy Mathe, Peng Dong, Su-Chen Huang, Maria Aurelia Ricci, Laura Baranello, Ying Zheng, Francesco Tomassoni Ardori, Wolfgang Resch, Diana Stavreva, Steevenson Nelson, Michael McAndrew, Adriel Casellas, Elizabeth Finn, Charles Gregory, Brian Glenn St Hilaire, Steven M Johnson, Wendy Dubois, Maria Pia Cosma, Eric Batchelor, David Levens, Robert D Phair, Tom Misteli, Lino Tessarollo, Gordon Hager, Melike Lakadamyali, Zhe Liu, Monique Floer, Hari Shroff, Erez Lieberman Aiden, Rafael Casellas
50 years ago, Vincent Allfrey and colleagues discovered that lymphocyte activation triggers massive acetylation of chromatin. However, the molecular mechanisms driving epigenetic accessibility are still unknown. We here show that stimulated lymphocytes decondense chromatin by three differentially regulated steps. First, chromatin is repositioned away from the nuclear periphery in response to global acetylation. Second, histone nanodomain clusters decompact into mononucleosome fibers through a mechanism that requires Myc and continual energy input...
August 17, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28802249/high-resolution-mapping-of-chromatin-conformation-in-cardiac-myocytes-reveals-structural-remodeling-of-the-epigenome-in-heart-failure
#16
Manuel Rosa-Garrido, Douglas J Chapski, Anthony D Schmitt, Todd H Kimball, Elaheh Karbassi, Emma Monte, Enrique Balderas, Matteo Pellegrini, Tsai-Ting Shih, Elizabeth Soehalim, David A Liem, Peipei Ping, Niels J Galjart, Shuxun Ren, Yibin Wang, Bing Ren, Thomas M Vondriska
Background -Cardiovascular disease is associated with epigenomic changes in the heart, however the endogenous structure of cardiac myocyte chromatin has never been determined. Methods -To investigate the mechanisms of epigenomic function in the heart, genome-wide chromatin conformation capture (Hi-C) and DNA sequencing were performed in adult cardiac myocytes following development of pressure overload-induced hypertrophy. Mice with cardiac-specific deletion of CTCF (a ubiquitous chromatin structural protein) were generated to explore the role of this protein in chromatin structure and cardiac phenotype...
August 11, 2017: Circulation
https://www.readbyqxmd.com/read/28801897/chromatin-immunoprecipitation-and-quantitative-real-time-pcr-to-assess-binding-of-a-protein-of-interest-to-identified-predicted-binding-sites-within-a-promoter
#17
Jordan E Read
Chromatin immunoprecipitation (ChIP) has become a widely used methodology for assessment of protein/DNA interactions. The technique allows the analysis of direct binding of transcription factors to gene promoters, identification of histone modifications, and localization of DNA modifying enzymes. Antibodies conjugated to agarose beads can be utilized to immunoprecipitate specific proteins, cross-linked to sheared chromatin regions to which they are bound endogenously. With downstream applications including quantitative real-time polymerase chain reaction (qRT-PCR), genome-wide sequencing (ChIP-seq), microarray analysis (ChIP-chip), and mass spectrometry (ChIP-MS), the technique enables comprehensive assessment of protein/DNA interactions...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28801756/segregation-distortion-and-genome-wide-digenic-interactions-affect-transmission-of-introgressed-chromatin-from-wild-cotton-species
#18
Rahul Chandnani, Baohua Wang, Xavier Draye, Lisa K Rainville, Susan Auckland, Zhimin Zhuang, Edward L Lubbers, O Lloyd May, Peng W Chee, Andrew H Paterson
This study reports transmission genetics of chromosomal segments into Gossypium hirsutum from its most distant euploid relative, Gossypium mustelinum . Mutilocus interactions and structural rearrangements affect introgression and segregation of donor chromatin. Wild allotetraploid relatives of cotton are a rich source of genetic diversity that can be used in genetic improvement, but linkage drag and non-Mendelian transmission genetics are prevalent in interspecific crosses. These problems necessitate knowledge of transmission patterns of chromatin from wild donor species in cultivated recipient species...
August 11, 2017: TAG. Theoretical and Applied Genetics. Theoretische und Angewandte Genetik
https://www.readbyqxmd.com/read/28801535/expansion-of-the-iswi-chromatin-remodeler-family-with-new-active-complexes
#19
Mariano Oppikofer, Tianyi Bai, Yutian Gan, Benjamin Haley, Peter Liu, Wendy Sandoval, Claudio Ciferri, Andrea G Cochran
ISWI chromatin remodelers mobilize nucleosomes to control DNA accessibility. Complexes isolated to date pair one of six regulatory subunits with one of two highly similar ATPases. However, we find that each endogenously expressed ATPase co-purifies with every regulatory subunit, substantially increasing the diversity of ISWI complexes, and we additionally identify BAZ2B as a novel, seventh regulatory subunit. Through reconstitution of catalytically active human ISWI complexes, we demonstrate that the new interactions described here are stable and direct...
August 11, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28801231/anti-inflammatory-chromatinscape-suggests-alternative-mechanisms-of-glucocorticoid-receptor-action
#20
Kyu-Seon Oh, Heta Patel, Rachel A Gottschalk, Wai Shing Lee, Songjoon Baek, Iain D C Fraser, Gordon L Hager, Myong-Hee Sung
Despite the widespread use of glucocorticoids (GCs), their anti-inflammatory effects are not understood mechanistically. Numerous investigations have examined the effects of glucocorticoid receptor (GR) activation prior to inflammatory challenges. However, clinical situations are emulated by a GC intervention initiated in the midst of rampant inflammatory responses. To characterize the effects of a late GC treatment, we profiled macrophage transcriptional and chromatinscapes with Dexamethasone (Dex) treatment before or after stimulation by lipopolysaccharide (LPS)...
August 15, 2017: Immunity
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