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Abstract
BORIS and CTCF are paralogous, multivalent 11-zinc finger transcription factors roles in organizing higher-order chromatin architecture. They are commonly altered in cancer. BORIS is a cancer-testis antigen with a poorly defined function in cancer, although it has been hypothesized to exhibit oncogenic properties. CTCF, however, has been postulated as a candidate tumor suppressor. We collated the genetic lesions in BORIS and CTCF from multiple cancers ...
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by Sangjin Kim, Erik Broströmer, Dong Xing, et al.Jianshi Jin, Shasha Chong, Hao Ge, Siyuan Wang, Chan Gu, Lijiang Yang, Yi Q. Gao, Xiao-dong Su, Yujie Sun, X. Sunney Xie
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posted to qpcr real-time-pcr
by sebastien_vigneau
on 2013-01-08 15:08:21
Abstract
Quantitative real-time polymerase chain reaction (qPCR) has been previously applied to estimate transgene copy number in transgenic plants. However, the results can be erroneous owing to inaccurate estimation of PCR efficiency. Here, a novel qPCR approach, named standard addition qPCR (SAQPCR), was devised to accurately determine transgene copy number without the necessity of obtaining PCR efficiency data. The procedures and the mathematical basis for the approach are described. A recombinant plasmid harboring both the internal reference gene and the integrated target ...
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by An Xiao, Yingdan Wu, Zhipeng Yang, et al.Yingying Hu, Weiye Wang, Yutian Zhang, Lei Kong, Ge Gao, Zuoyan Zhu, Shuo Lin, Bo Zhang
Abstract
We report here the construction of engineered endonuclease database (EENdb) (http://eendb.zfgenetics.org/), a searchable database and knowledge base for customizable engineered endonucleases (EENs), including zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs). EENs are artificial nucleases designed to target and cleave specific DNA sequences. EENs have been shown to be a very useful genetic tool for targeted genome modification and have shown great potentials in the applications in basic research, clinical therapies and agricultural utilities, and they are specifically essential ...
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by Jie Wang, Jiali Zhuang, Sowmya Iyer, et al.Xin-Ying Lin, Melissa C. Greven, Bong-Hyun Kim, Jill Moore, Brian G. Pierce, Xianjun Dong, Daniel Virgil, Ewan Birney, Jui-Hung Hung, Zhiping Weng
Abstract
The Encyclopedia of DNA Elements (ENCODE) consortium aims to identify all functional elements in the human genome including transcripts, transcriptional regulatory regions, along with their chromatin states and DNA methylation patterns. The ENCODE project generates data utilizing a variety of techniques that can enrich for regulatory regions, such as chromatin immunoprecipitation (ChIP), micrococcal nuclease (MNase) digestion and DNase I digestion, followed by deeply sequencing the resulting DNA. As part of the ENCODE project, we have developed a Web-accessible repository accessible at ...
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Abstract
Telomere extension by telomerase is essential for chromosome stability and cell vitality. Here, we report the identification of a splice variant of mammalian heterogeneous nuclear ribonucleoprotein A2 (hnRNP A2), hnRNP A2*, which binds telomeric DNA and telomerase in vitro. hnRNP A2* colocalizes with telomerase in Cajal bodies and at telomeres. In vitro assays show that hnRNP A2* actively unfolds telomeric G-quadruplex DNA, exposes 5 nt ...
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by Zhong Deng, Zhuo Wang, Nick Stong, et al.Robert Plasschaert, Aliah Moczan, Horng-Shen S. Chen, Sufeng Hu, Priyankara Wikramasinghe, Ramana V. Davuluri, Marisa S. Bartolomei, Harold Riethman, Paul M. Lieberman
posted to cohesin ctcf
by sebastien_vigneau
on 2012-10-02 20:17:20
Abstract
The contribution of human subtelomeric DNA and chromatin organization to telomere integrity and chromosome end protection is not yet understood in molecular detail. Here, we show by ChIP-Seq that most human subtelomeres contain a CTCF- and cohesin-binding site within ∼1-2 kb of the TTAGGG repeat tract and adjacent to a CpG-islands implicated in TERRA transcription control. ChIP-Seq also revealed that RNA polymerase II (RNAPII) was enriched ...
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Abstract
The average individual is expected to harbor thousands of variants within non-coding genomic regions involved in gene regulation. However, it is currently not possible to interpret reliably the functional consequences of genetic variation within any given transcription factor recognition sequence. To address this, we comprehensively analyzed heritable genome-wide binding patterns of a major sequence-specific regulator (CTCF) in relation to genetic variability in binding site sequences across a multi-generational pedigree. We localized and quantified CTCF occupancy by ChIP-seq in 12 related and ...
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Abstract
Retinoic acid, an active metabolite of vitamin A, plays essential signaling roles in mammalian embryogenesis. Nevertheless, it has long been recognized that overexposure to vitamin A or retinoic acid causes widespread teratogenesis in rodents as well as humans. Although it has a short half-life, exposure to high levels of retinoic acid can disrupt development of yet-to-be formed organs, including the metanephros, the embryonic organ which ...
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Abstract
Chromatin insulators are DNA elements that regulate the level of gene expression either by preventing gene silencing through the maintenance of heterochromatin boundaries or by preventing gene activation by blocking interactions between enhancers and promoters. CCCTC-binding factor (CTCF), a ubiquitously expressed 11-zinc-finger DNA-binding protein, is the only protein implicated in the establishment of insulators in vertebrates. While CTCF has been implicated in diverse regulatory functions, CTCF has only been studied in a limited number of cell types across human genome. Thus, ...
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Abstract
We have analyzed publicly available K562 Hi-C data, which enable genome-wide unbiased capturing of chromatin interactions, using a Mixture Poisson Regression Model and a power-law decay background to define a highly specific set of interacting genomic regions. We integrated multiple ENCODE Consortium resources with the Hi-C data, using DNase-seq data and ChIP-seq data for 45 transcription factors and 9 histone modifications. We classified 12 different ...
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Abstract
We trained Segway, a dynamic Bayesian network method, simultaneously on chromatin data from multiple experiments, including positions of histone modifications, transcription-factor binding and open chromatin, all derived from a human chronic myeloid leukemia cell line. In an unsupervised fashion, we identified patterns associated with transcription start sites, gene ends, enhancers, transcriptional regulator CTCF-binding regions and repressed regions. Software and genome browser tracks are at http://noble.gs.washington.edu/proj/segway/. ...
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Abstract
Attempts to generate reliable and versatile vectors for gene therapy and biomedical research that express multiple genes have met with limited success. Here we used Picornavirus 'self-cleaving' 2A peptides, or 2A-like sequences from other viruses, to generate multicistronic retroviral vectors with efficient translation of four cistrons. Using the T-cell receptor:CD3 complex as a test system, we show that a single 2A peptide-linked retroviral vector can ...
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Abstract
Long noncoding RNAs (lncRNAs) have important regulatory roles and can function at the level of chromatin. To determine where lncRNAs bind to chromatin, we developed capture hybridization analysis of RNA targets (CHART), a hybridization-based technique that specifically enriches endogenous RNAs along with their targets from reversibly cross-linked chromatin extracts. CHART was used to enrich the DNA and protein targets of endogenous lncRNAs from flies and humans. This analysis was extended to genome-wide mapping of roX2, a well-studied ncRNA involved in dosage ...
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Abstract
Optimization of primer sequences for polymerase chain reaction (PCR) and quantitative PCR (qPCR) and reaction conditions remains an experimental challenge. We have developed a resource, PrimerBank, which contains primers that can be used for PCR and qPCR under stringent and allele-invariant amplification conditions. A distinguishing feature of PrimerBank is the experimental validation of primer pairs covering most known mouse genes. Here, we describe a major update of PrimerBank that includes the design of new primers covering 17 076 and 18 086 genes for ...
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Abstract
CCCTC-binding factor (CTCF) is a master organizer of genome spatial organization and plays an important role in mediating extensive chromatin interactions. Circular chromosome conformation capture (4C) is a high-throughput approach that allows genome-wide screening for unknown potential interaction partners. Using a conserved CTCF binding site on the Bcl11b locus as bait, an interaction partner at the Arhgap6 locus on a different chromosome was identified by ...
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Abstract
Boundary elements partition eukaryotic chromatin into active and repressive domains, and can also block regulatory interactions between domains. Boundary elements act via diverse mechanisms making accurate feature-based computational predictions difficult. Therefore, we developed an unbiased algorithm that predicts the locations of human boundary elements based on the genomic distributions of chromatin and transcriptional states, as opposed to any intrinsic characteristics that they may possess. Application ...
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Abstract
Many questions about the regulation, functional specialization, computational prediction, and evolution of genomic imprinting would be better addressed by having an exhaustive genome-wide catalog of genes that display parent-of-origin differential expression. As a first-pass scan for novel imprinted genes, we performed mRNA-seq experiments on embryonic day 17.5 (E17.5) mouse placenta cDNA samples from reciprocal cross F1 progeny of AKR and PWD mouse strains and quantified the allele-specific expression and the degree of parent-of-origin allelic imbalance. We confirmed the imprinting status of ...
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Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, No. 37. (13 September 2011), pp. 15231-15236, doi:10.1073/pnas.1104662108
by Ming Tang, Bo Chen, Tong Lin, et al.Zhaozhong Li, Carolina Pardo, Christine Pampo, Jing Chen, Ching-Ling L. Lien, Lizi Wu, Lingbao Ai, Heiman Wang, Kai Yao, S. Paul Oh, Edward Seto, Lois E. Smith, Dietmar W. Siemann, Michael P. Kladde, Constance L. Cepko, Jianrong Lu
Abstract
Angiogenesis is meticulously controlled by a fine balance between positive and negative regulatory activities. Vascular endothelial growth factor (VEGF) is a predominant angiogenic factor and its dosage is precisely regulated during normal vascular formation. In cancer, VEGF is commonly overproduced, resulting in abnormal neovascularization. VEGF is induced in response to various stimuli including hypoxia; however, very little is known about the mechanisms that confine its ...
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by Farren J. Isaacs, Peter A. Carr, Harris H. Wang, et al.Marc J. Lajoie, Bram Sterling, Laurens Kraal, Andrew C. Tolonen, Tara A. Gianoulis, Daniel B. Goodman, Nikos B. Reppas, Christopher J. Emig, Duhee Bang, Samuel J. Hwang, Michael C. Jewett, Joseph M. Jacobson, George M. Church
Abstract
We present genome engineering technologies that are capable of fundamentally reengineering genomes from the nucleotide to the megabase scale. We used multiplex automated genome engineering (MAGE) to site-specifically replace all 314 TAG stop codons with synonymous TAA codons in parallel across 32 Escherichia coli strains. This approach allowed us to measure individual recombination frequencies, confirm viability for each modification, and identify associated phenotypes. We developed hierarchical conjugative assembly genome engineering (CAGE) to merge these sets of codon modifications into genomes with ...
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Abstract
Poly adenosine diphosphate (ADP)–ribosylation (PARylation) by poly ADP-ribose (PAR) polymerases (PARPs) is an early response to DNA double-strand breaks (DSBs). In this paper, we exploit Dictyostelium discoideum to uncover a novel role for PARylation in regulating nonhomologous end joining (NHEJ). PARylation occurred at single-strand breaks, and two PARPs, Adprt1b and Adprt2, were required for resistance to this kind of DNA damage. In contrast, although Adprt1b was dispensable for PARylation at DSBs, Adprt1a and, to a lesser extent, Adprt2 were required for ...
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Abstract
The transmission of information from DNA to RNA is a critical process. We compared RNA sequences from human B cells of 27 individuals to the corresponding DNA sequences from the same individuals and uncovered more than 10,000 exonic sites where the RNA sequences do not match that of the DNA. All 12 possible categories of discordances were observed. These differences were nonrandom as many sites ...
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Abstract
Chromatin immunoprecipitation (ChIP) coupled with high-throughput techniques (ChIP-X), such as next generation sequencing (ChIP-Seq) and microarray (ChIP-chip), has been successfully used to map active transcription factor binding sites (TFBS) of a transcription factor (TF). The targeted genes can be activated or suppressed by the TF, or are unresponsive to the TF. Microarray technology has been used to measure the actual expression changes of thousands of genes under the perturbation of a TF, but is unable to determine if the affected genes ...
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Abstract
The widespread natural ability of RNA to sense small molecules and regulate genes has become an important tool for synthetic biology in applications as diverse as environmental sensing and metabolic engineering. Previous work in RNA synthetic biology has engineered RNA mechanisms that independently regulate multiple targets and integrate regulatory signals. However, intracellular regulatory networks built with these systems have required proteins to propagate regulatory signals. In this work, we remove this requirement and expand the RNA synthetic biology toolkit by engineering ...
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by Dong Wang, Ivan Garcia-Bassets, Chris Benner, et al.Wenbo Li, Xue Su, Yiming Zhou, Jinsong Qiu, Wen Liu, Minna U. Kaikkonen, Kenneth A. Ohgi, Christopher K. Glass, Michael G. Rosenfeld, Xiang-Dong Fu
Abstract
Mammalian genomes are populated with thousands of transcriptional enhancers that orchestrate cell-type-specific gene expression programs, but how those enhancers are exploited to institute alternative, signal-dependent transcriptional responses remains poorly understood. Here we present evidence that cell-lineage-specific factors, such as FoxA1, can simultaneously facilitate and restrict key regulated transcription factors, exemplified by the androgen receptor (AR), to act on structurally and functionally distinct classes of enhancer. Consequently, FoxA1 downregulation, an unfavourable prognostic sign in certain advanced prostate tumours, triggers dramatic reprogramming of ...
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Abstract
We implement a unique strategy for single molecule counting termed stochastic labeling, where random attachment of a diverse set of labels converts a population of identical DNA molecules into a population of distinct DNA molecules suitable for threshold detection. The conceptual framework for stochastic labeling is developed and experimentally demonstrated by determining the absolute and relative number of selected genes after stochastically labeling approximately 360,000 different fragments of the human genome. The approach does not require the physical separation of molecules ...
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Abstract
We developed a theoretical framework to prove the existence and quantify the Waddington landscape as well as chreode-biological paths for development and differentiation. The cells can have states with the higher probability ones giving the different cell types. Different cell types correspond to different basins of attractions of the probability landscape. We study how the cells develop from undifferentiated cells to differentiated cells from landscape perspectives. We quantified the Waddington landscape through construction of underlying probability landscape for cell development. We ...
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Abstract
Monoallelic expression of IGF2 is regulated by CCCTC binding factor (CTCF) binding to the imprinting control region (ICR) on the maternal allele, with subsequent formation of an intrachromosomal loop to the promoter region. The N-terminal domain of CTCF interacts with SUZ12, part of the polycomb repressive complex-2 (PRC2), to silence the maternal allele. We synthesized decoy CTCF proteins, fusing the CTCF deoxyribonucleic acid-binding zinc finger ...
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by Wenlin Li, Woong Sun, Yu Zhang, et al.Wanguo Wei, Rajesh Ambasudhan, Peng Xia, Maria Talantova, Tongxiang Lin, Janghwan Kim, Xiaolei Wang, Woon R. Kim, Stuart A. Lipton, Kang Zhang, Sheng Ding
Abstract
Human embryonic stem cells (hESCs) hold enormous promise for regenerative medicine. Typically, hESC-based applications would require their in vitro differentiation into a desirable homogenous cell population. A major challenge of the current hESC differentiation paradigm is the inability to effectively capture and, in the long-term, stably expand primitive lineage-specific stem/precursor cells that retain broad differentiation potential and, more importantly, developmental stage-specific differentiation propensity. Here, we report synergistic inhibition of glycogen synthase kinase 3 (GSK3), transforming growth factor β (TGF-β), and Notch ...
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Abstract
Gene expression noise is a universal phenomenon across all life forms. Although beneficial under certain circumstances, expression noise is generally thought to be deleterious. However, neither the magnitude of the deleterious effect nor the primary mechanism of this effect is known. Here, we model the impact of expression noise on the fitness of unicellular organisms by considering the influence of suboptimal expressions of enzymes on the rate of biomass production and the energetic cost associated with imprecise amounts of protein synthesis. ...
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Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, No. 19. (10 May 2011), pp. 7838-7843, doi:10.1073/pnas.1103113108
Abstract
The simple yet powerful technique of induced pluripotency may eventually supply a wide range of differentiated cells for cell therapy and drug development. However, making the appropriate cells via induced pluripotent stem cells (iPSCs) requires reprogramming of somatic cells and subsequent redifferentiation. Given how arduous and lengthy this process can be, we sought to determine whether it might be possible to convert somatic cells into lineage-specific stem/progenitor cells of another germ layer in one step, bypassing the intermediate pluripotent stage. Here ...
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posted to splicing
by sebastien_vigneau
on 2011-04-27 21:53:11
Abstract
Alternative splicing is a process to differentially link exon regions in a single precursor mRNA to produce two or more different mature mRNAs, a strategy frequently used by higher eukaryotic cells to increase proteome diversity and/or enable additional post-transcriptional control of gene expression. This process can take place either co-transcriptionally or post-transcriptionally. When and where RNA splicing takes place in the cell represents a central question of cell biology; co-transcriptionally splicing allows functional integration of transcription and RNA processing machineries, and ...
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Abstract
Most transcripts in growing cells are ribosomal RNA precursors (pre-rRNA). Here, we show that in mammals, aberrant pre-rRNA transcripts generated by RNA polymerase I (Pol I) are polyadenylated and accumulate markedly after treatment with low concentrations of actinomycin D (ActD), which blocks the synthesis of full-length rRNA. The poly(A) polymerase-associated domain-containing protein 5 is required for polyadenylation, whereas the exosome is partly responsible for the degradation of the short aberrant transcripts. Thus, polyadenylation functions in the quality control of Pol I ...
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by Yang Wang, Jiekai Chen, Jia-Lei L. Hu, et al.Xi-Xiao X. Wei, Dajiang Qin, Juan Gao, Lei Zhang, Jing Jiang, Jin-Song S. Li, Jing Liu, Ke-Yu Y. Lai, Xia Kuang, Jian Zhang, Duanqing Pei, Guo-Liang L. Xu
posted to ipsc reprogramming
by sebastien_vigneau
on 2011-04-18 19:15:27
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Abstract
During the transition from the inner cell mass (ICM) cells of blastocysts to pluripotent embryonic stem cells (ESCs) in vitro, a normal developmental program is replaced in cells that acquire a capacity for infinite self-renewal and pluripotency. We explored the underlying mechanism of this switch by using RNA-Seq transcriptome analysis at the resolution of single cells. We detected significant molecular transitions and major changes in ...
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by Chia L. Wei, Takumi Miura, Paul Robson, et al.Sai-Kiang Lim, Xiu-Qin Xu, Mathia Y. Lee, Sanjay Gupta, Lawrence Stanton, Yongquan Luo, Jacqui Schmitt, Scott Thies, Wei Wang, Irina Khrebtukova, Daixing Zhou, Edison T. Liu, Yi J. Ruan, Mahendra Rao, Bing Lim
Abstract
Human embryonic stem cells (hESCs) are an important source of stem cells in regenerative medicine, and much remains unknown about their molecular characteristics. To develop a detailed genomic profile of ESC lines in two different species, we compared transcriptomes of one murine and two different hESC lines by massively parallel signature sequencing (MPSS). Over 2 million signature tags from each line and their differentiating embryoid bodies were sequenced. Major differences and conserved similarities between species identified by MPSS were validated by ...
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Abstract
Through alternative splicing, most human genes express multiple isoforms that often differ in function. To infer isoform regulation from high-throughput sequencing of cDNA fragments (RNA-seq), we developed the mixture-of-isoforms (MISO) model, a statistical model that estimates expression of alternatively spliced exons and isoforms and assesses confidence in these estimates. Incorporation of mRNA fragment length distribution in paired-end RNA-seq greatly improved estimation of alternative-splicing levels. MISO ...
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by Yang Wang, Jiekai Chen, Jia-Lei L. Hu, et al.Xi-Xiao X. Wei, Dajiang Qin, Juan Gao, Lei Zhang, Jing Jiang, Jin-Song S. Li, Jing Liu, Ke-Yu Y. Lai, Xia Kuang, Jian Zhang, Duanqing Pei, Guo-Liang L. Xu
Abstract
Reprogramming somatic cells to become induced pluripotent stem cells (iPSCs) by using defined factors represents an important breakthrough in biology and medicine, yet remains inefficient and poorly understood. We therefore devised synthetic factors by fusing the VP16 transactivation domain to OCT4 (also known as Pou5f1), NANOG and SOX2, respectively. These synthetic factors could reprogramme both mouse and human fibroblasts with enhanced efficiency and accelerated kinetics. Remarkably, Oct4-VP16 alone could efficiently reprogramme mouse embryonic fibroblasts (MEFs) into germline-competent iPSCs. Furthermore, episomally delivered ...
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Abstract
Although regulation of histone methylation is believed to contribute to embryonic stem cell (ESC) self-renewal, the mechanisms remain obscure. We show here that the histone H3 trimethyl lysine 4 (H3K4me3) demethylase, KDM5B, is a downstream Nanog target and critical for ESC self-renewal. Although KDM5B is believed to function as a promoter-bound repressor, we find that it paradoxically functions as an activator of a gene network associated with self-renewal. ChIP-Seq reveals that KDM5B is predominantly targeted to intragenic regions and that it ...
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Journal of bioinformatics and computational biology, Vol. 8 Suppl 1 (December 2010), pp. 177-192
Abstract
Due to its unprecedented high-resolution and detailed information, RNA-seq technology based on next-generation high-throughput sequencing significantly boosts the ability to study transcriptomes. The estimation of genes' transcript abundance levels or gene expression levels has always been an important question in research on the transcriptional regulation and gene functions. On the basis of the concept of Reads Per Kilo-base per Million reads (RPKM), taking the union-intersection genes (UI-based) and summing up inferred isoform abundance (isoform-based) are the two current strategies to estimate ...
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Abstract
Zinc-finger nucleases (ZFNs) drive efficient genome editing by introducing a double-strand break into the targeted gene. Cleavage is induced when two custom-designed ZFNs heterodimerize upon binding DNA to form a catalytically active nuclease complex. The importance of this dimerization event for subsequent cleavage activity has stimulated efforts to engineer the nuclease interface to prevent undesired homodimerization. Here we report the development and application of a yeast-based selection system designed to functionally interrogate the ZFN dimer interface. We identified critical residues involved ...
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by Akira Nishiyama, Li Xin, Alexei A. Sharov, et al.Marshall Thomas, Gregory Mowrer, Emily Meyers, Yulan Piao, Samir Mehta, Sarah Yee, Yuhki Nakatake, Carole Stagg, Lioudmila Sharova, Lina S. Correa-Cerro, Uwem Bassey, Hien Hoang, Eugene Kim, Richard Tapnio, Yong Qian, Dawood Dudekula, Michal Zalzman, Manxiang Li, Geppino Falco, Hsih-Te T. Yang, Sung-Lim L. Lee, Manuela Monti, Ilaria Stanghellini, Md Nurul N. Islam, Ramaiah Nagaraja, Ilya Goldberg, Weidong Wang, Dan L. Longo, David Schlessinger, Minoru S. Ko
Abstract
To examine transcription factor (TF) network(s), we created mouse ESC lines, in each of which 1 of 50 TFs tagged with a FLAG moiety is inserted into a ubiquitously controllable tetracycline-repressible locus. Of the 50 TFs, Cdx2 provoked the most extensive transcriptome perturbation in ESCs, followed by Esx1, Sox9, Tcf3, Klf4, and Gata3. ChIP-Seq revealed that CDX2 binds to promoters of upregulated target genes. By contrast, genes downregulated by CDX2 did not show CDX2 binding but were enriched with binding sites ...
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Abstract
The functional structure of all biologically active molecules is dependent on intra- and inter-molecular interactions. This is especially evident for RNA molecules whose functionality, maturation, and regulation require formation of correct secondary structure through encoded base-pairing interactions. Unfortunately, intra- and inter-molecular base-pairing information is lacking for most RNAs. Here, we marry classical nuclease-based structure mapping techniques with high-throughput sequencing technology to interrogate all base-paired RNA in Arabidopsis thaliana and identify ~200 new small (sm)RNA–producing substrates of RNA–DEPENDENT RNA POLYMERASE6. Our comprehensive ...
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Abstract
Methylation of histone H3K36 in higher eukaryotes is mediated by multiple methyltransferases. Set2-related H3K36 methyltransferases are targeted to genes by association with RNA Polymerase II and are involved in preventing aberrant transcription initiation within the body of genes. The targeting and roles of the NSD family of mammalian H3K36 methyltransferases, known to be involved in human developmental disorders and oncogenesis, are not known. We used genome-wide chromatin immunoprecipitation (ChIP) to investigate the targeting and roles of the Caenorhabditis elegans NSD homolog ...
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Abstract
Unlike autosomal genes, the majority of X-linked genes are subject to dosage compensation. As a result, female tissues comprise cells exclusively expressing X-linked genes from one or other parent. The implication of having only one allele of active X-linked genes in cancer pathogenesis, i.e. somatic single-hit inactivation and dominant inheritance, has not been extensively explored. Recent studies have identified FOXP3 and WTX as two X-linked ...
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Abstract
Alternative splicing has a crucial role in the generation of biological complexity, and its misregulation is often involved in human disease. Here we describe the assembly of a ‘splicing code’, which uses combinations of hundreds of RNA features to predict tissue-dependent changes in alternative splicing for thousands of exons. The code determines new classes of splicing patterns, identifies distinct regulatory programs in different tissues, and identifies mutation-verified regulatory sequences. Widespread regulatory strategies are revealed, including the use of unexpectedly large combinations ...
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by Hui Liu, Jing Huang, Jin Wang, et al.Shuguang Jiang, Alexis S. Bailey, Devorah C. Goldman, Markus Welcker, Victoria Bedell, Marilyn L. Slovak, Bruce Clurman, Mathew Thayer, William H. Fleming, Elliot Epner
Abstract
In mantle cell lymphoma (MCL) and some cases of multiple myeloma (MM), cyclin D1 expression is deregulated by chromosome translocations involving the immunoglobulin heavy chain (IgH) locus. To evaluate the mechanisms responsible, gene targeting was used to study long-distance gene regulation. Remarkably, these targeted cell lines lost the translocated chromosome (t(11;14)). In these MCL and MM cells, the nonrearranged cyclin D1 (CCND1) locus reverts from CpG hypomethylated to hypermethylated. Reintroduction of the translocated chromosome induced a loss of methylation at the ...
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Abstract
In many bacteria, there is a genome-wide bias towards co-orientation of replication and transcription, with essential and/or highly-expressed genes further enriched co-directionally. We previously found that reversing this bias in the bacterium Bacillus subtilis slows replication elongation, and we proposed that this effect contributes to the evolutionary pressure selecting the transcription-replication co-orientation bias. This selection might have been based purely on selection for speedy replication; alternatively, the slowed replication might actually represent an average of individual replication-disruption events, each of which ...
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