| 1. |
- Ramilowski, JA, et al.
(författare)
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Functional annotation of human long noncoding RNAs via molecular phenotyping
- 2020
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Ingår i: Genome research. - : Cold Spring Harbor Laboratory. - 1549-5469 .- 1088-9051. ; 30:7, s. 1060-1072
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Tidskriftsartikel (refereegranskat)abstract
- Long noncoding RNAs (lncRNAs) constitute the majority of transcripts in the mammalian genomes, and yet, their functions remain largely unknown. As part of the FANTOM6 project, we systematically knocked down the expression of 285 lncRNAs in human dermal fibroblasts and quantified cellular growth, morphological changes, and transcriptomic responses using Capped Analysis of Gene Expression (CAGE). Antisense oligonucleotides targeting the same lncRNAs exhibited global concordance, and the molecular phenotype, measured by CAGE, recapitulated the observed cellular phenotypes while providing additional insights on the affected genes and pathways. Here, we disseminate the largest-to-date lncRNA knockdown data set with molecular phenotyping (over 1000 CAGE deep-sequencing libraries) for further exploration and highlight functional roles for ZNF213-AS1 and lnc-KHDC3L-2.
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| 2. |
- Ho, Joshua W. K., et al.
(författare)
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Comparative analysis of metazoan chromatin organization
- 2014
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 512:7515, s. 449-U507
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Tidskriftsartikel (refereegranskat)abstract
- Genome function is dynamically regulated in part by chromatin, which consists of the histones, non-histone proteins and RNA molecules that package DNA. Studies in Caenorhabditis elegans and Drosophila melanogaster have contributed substantially to our understanding of molecular mechanisms of genome function in humans, and have revealed conservation of chromatin components and mechanisms(1-3). Nevertheless, the three organisms have markedly different genome sizes, chromosome architecture and gene organization. On human and fly chromosomes, for example, pericentric heterochromatin flanks single centromeres, whereas worm chromosomes have dispersed heterochromatin-like regions enriched in the distal chromosomal 'arms', and centromeres distributed along their lengths(4,5). To systematically investigate chromatin organization and associated gene regulation across species, we generated and analysed a large collection of genome-wide chromatin data sets from cell lines and developmental stages in worm, fly and human. Here we present over 800 new data sets from our ENCODE and modENCODE consortia, bringing the total to over 1,400. Comparison of combinatorial patterns of histone modifications, nuclear lamina-associated domains, organization of large-scale topological domains, chromatin environment at promoters and enhancers, nucleosome positioning, and DNA replication patterns reveals many conserved features of chromatin organization among the three organisms. We also find notable differences in the composition and locations of repressive chromatin. These data sets and analyses provide a rich resource for comparative and species-specific investigations of chromatin composition, organization and function.
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| 3. |
- Roy, Sushmita, et al.
(författare)
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Identification of functional elements and regulatory circuits by Drosophila modENCODE.
- 2010
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 330:6012, s. 1787-1797
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Tidskriftsartikel (refereegranskat)abstract
- To gain insight into how genomic information is translated into cellular and developmental programs, the Drosophila model organism Encyclopedia of DNA Elements (modENCODE) project is comprehensively mapping transcripts, histone modifications, chromosomal proteins, transcription factors, replication proteins and intermediates, and nucleosome properties across a developmental time course and in multiple cell lines. We have generated more than 700 data sets and discovered protein-coding, noncoding, RNA regulatory, replication, and chromatin elements, more than tripling the annotated portion of the Drosophila genome. Correlated activity patterns of these elements reveal a functional regulatory network, which predicts putative new functions for genes, reveals stage- and tissue-specific regulators, and enables gene-expression prediction. Our results provide a foundation for directed experimental and computational studies in Drosophila and related species and also a model for systematic data integration toward comprehensive genomic and functional annotation.
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| 4. |
- Kharchenko, Peter V, et al.
(författare)
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Comprehensive analysis of the chromatin landscape in Drosophila melanogaster
- 2011
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 471:7339, s. 480-485
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Tidskriftsartikel (refereegranskat)abstract
- Chromatin is composed of DNA and a variety of modified histones and non-histone proteins, which have an impact on cell differentiation, gene regulation and other key cellular processes. Here we present a genome-wide chromatin landscape for Drosophila melanogaster based on eighteen histone modifications, summarized by nine prevalent combinatorial patterns. Integrative analysis with other data (non-histone chromatin proteins, DNase I hypersensitivity, GRO-Seq reads produced by engaged polymerase, short/long RNA products) reveals discrete characteristics of chromosomes, genes, regulatory elements and other functional domains. We find that active genes display distinct chromatin signatures that are correlated with disparate gene lengths, exon patterns, regulatory functions and genomic contexts. We also demonstrate a diversity of signatures among Polycomb targets that include a subset with paused polymerase. This systematic profiling and integrative analysis of chromatin signatures provides insights into how genomic elements are regulated, and will serve as a resource for future experimental investigations of genome structure and function.
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| 5. |
- Zhou, Qi, et al.
(författare)
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Phase transition of thermosensitive amphiphilic cellulose esters bearing olig(oxyethylene)s
- 2000
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Ingår i: Polymer Bulletin. - : Springer Science and Business Media LLC. - 0170-0839 .- 1436-2449. ; 45:05-apr, s. 381-388
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Tidskriftsartikel (refereegranskat)abstract
- A series of cellulose esters bearing olig(oxyethylene)s with different degree of substitution (DS) and different length of the oxyethylene chain were synthesized by a homogeneous reaction of cellulose with corresponding monofunctional acid chloride in a 10% LiCl-dimethyl acetoamide (DMAc) solution. The effect of total DS value on the solubility of the derivatives in aqueous solution was investigated. It was found that the lower limit DS value for both water-soluble and amphiphilic derivatives decreases with increasing length of oxyethylene chains. The amphiphilic derivatives, which are soluble in both water and chloroform, precipitate out of aqueous solution on heating without gel forming, such a phase transition behavior was studied in terms of DS value, length of oxyethylene and concentration. The precipitation temperature (T-p) of the amphiphilic derivatives is range from 54 degreesC to 96 degreesC. It decreases with increasing the total DS value, and increases with an increase in the length of oxyethylene chains. The T-p value of the derivatives was found to be almost independent in the concentration range of 1-15 wt %, however the T-p value increases sharply with decreasing polymer concentration when the concentration is lower than 1 wt%.
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| 6. |
- Zhou, Qi, et al.
(författare)
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Synthesis and properties of O-2- 2-(2-methoxyethoxy) ethoxy acetyl cellulose
- 2001
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Ingår i: Journal of Polymer Science Part A. - 0887-624X .- 1099-0518. ; 39:3, s. 376-382
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Tidskriftsartikel (refereegranskat)abstract
- In this article, a series of O-2-[2-(2-methoxyethoxy)ethoxy] acetyl celluloses with different degree of substitution (DS) values was synthesized by a homogeneous reaction of cellulose with 2-[2-(2-methoxyethoxy)ethoxy] acetyl chloride in a 10% (w/w) dimethylacetamide/lithium chloride solution, combined with pyridine as the acid acceptor. The total DS values of the derivatives in anhydroglucose units was determined by H-1 and C-13 NMR spectra, and ranged from 0.4 to 3.0, depending on the amount of acid chloride in the reaction. The effects of the total DS values and the O-2-[2-(2-methoxyethoxy)ethoxy]acetyl acetyl substituent distribution on the solubility of the derivatives were investigated. The lowest limit of the DS value for water-soluble 0-2-[2-(2methoxyethoxy)ethoxy]acetyl cellulose was approximately 0.5, which is lower than that of methylcellulose. The amphiphilic derivatives with higher DS values than 1.7 exhibited a good solubility in both water and organic solvents, such as dimethyl sulfoxide, tetrahydrofuran, and chloroform. Sol-gel transition in aqueous solution was observed for the amphiphilic derivatives with a higher DS value than 1.7; the precipitation temperature (T-p) decreased as the DS value increased, showing that the derivatives are highly temperature sensitive. The thermal properties of the fully substituted derivative were measured using polarized microscopy, DSC, and X-ray diffraction; and are dis cussed in terms of phase transition of the sample derivatives.
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