共查询到20条相似文献,搜索用时 31 毫秒
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Separation of transcriptional activation and silencing functions of the RAP1-encoded repressor/activator protein 1: isolation of viable mutants affecting both silencing and telomere length 总被引:40,自引:0,他引:40 下载免费PDF全文
L Sussel D Shore 《Proceedings of the National Academy of Sciences of the United States of America》1991,88(17):7749-7753
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Lysine-79 of histone H3 is hypomethylated at silenced loci in yeast and mammalian cells: a potential mechanism for position-effect variegation 总被引:26,自引:0,他引:26 下载免费PDF全文
Ng HH Ciccone DN Morshead KB Oettinger MA Struhl K 《Proceedings of the National Academy of Sciences of the United States of America》2003,100(4):1820-1825
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Osborne EA Hiraoka Y Rine J 《Proceedings of the National Academy of Sciences of the United States of America》2011,108(4):1209-1216
In Saccharomyces cerevisiae, silent chromatin inhibits the expression of genes at the HML, HMR, and telomeric loci. When silent chromatin forms de novo, the rate of its establishment is influenced by different chromatin states. In particular, loss of the enzyme Dot1, an H3 K79 methyltransferase, leads to rapid silencing establishment. We tested whether silencing establishment was antagonized by H3 K79 methylation or by the Dot1 protein itself competing with Sir3 for binding sites on nucleosomes. To do so, we monitored fluorescence activity in cells containing a GFP gene within the HML locus during silencing establishment in a series of dot1 and histone mutant backgrounds. Silencing establishment rate was correlated with Dot1's enzymatic function rather than with the Dot1 protein itself. In addition, histone mutants that mimicked the conformation of unmethylated H3 K79 increased the rate of silencing establishment, indicating that the H3 K79 residue affected silencing independently of Dot1 abundance. Using fluorophore-based reporters, we confirmed that mother and daughter cells often silence in concert, but in instances where asymmetric silencing occurs, daughter cells established silencing earlier than their mothers. This noninvasive technique enabled us to demonstrate an asymmetry in silencing establishment of a key regulatory locus controlling cell fate. 相似文献
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MF Sentmanat SC Elgin 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(35):14104-14109
A persistent question in biology is how cis-acting sequence elements influence trans-acting factors and the local chromatin environment to modulate gene expression. We reported previously that the DNA transposon 1360 can enhance silencing of a reporter in a heterochromatic domain of Drosophila melanogaster. We have now generated a collection of variegating phiC31 landing-pad insertion lines containing 1360 and a heat-shock protein 70 (hsp70)-driven white reporter to explore the mechanism of 1360-sensitive silencing. Many 1360-sensitive sites were identified, some in apparently euchromatic domains, although all are close to heterochromatic masses. One such site (line 1198; insertion near the base of chromosome arm 2L) has been investigated in detail. ChIP analysis shows 1360-dependent Heterochromatin Protein 1a (HP1a) accumulation at this otherwise euchromatic site. The phiC31 landing pad system allows different 1360 constructs to be swapped with the full-length element at the same genomic site to identify the sequences that mediate 1360-sensitive silencing. Short deletions over sites with homology to PIWI-interacting RNAs (piRNAs) are sufficient to compromise 1360-sensitive silencing. Similar results were obtained on replacing 1360 with Invader4 (a retrotransposon), suggesting that this phenomenon likely applies to a broader set of transposable elements. Our results suggest a model in which piRNA sequence elements behave as cis-acting targets for heterochromatin assembly, likely in the early embryo, where piRNA pathway components are abundant, with the heterochromatic state subsequently propagated by chromatin modifiers present in somatic tissue. 相似文献
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Zhang F Thornhill SI Howe SJ Ulaganathan M Schambach A Sinclair J Kinnon C Gaspar HB Antoniou M Thrasher AJ 《Blood》2007,110(5):1448-1457
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Michael L. Beshiri Katherine B. Holmes William F. Richter Samuel Hess Abul B. M. M. K. Islam Qin Yan Lydia Plante Larisa Litovchick Nicolas Gévry Nuria Lopez-Bigas William G. Kaelin Jr. Elizaveta V. Benevolenskaya 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(45):18499-18504
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Sabo PJ Hawrylycz M Wallace JC Humbert R Yu M Shafer A Kawamoto J Hall R Mack J Dorschner MO McArthur M Stamatoyannopoulos JA 《Proceedings of the National Academy of Sciences of the United States of America》2004,101(48):16837-16842
We developed a quantitative methodology, digital analysis of chromatin structure (DACS), for high-throughput, automated mapping of DNase I-hypersensitive sites and associated cis-regulatory sequences in the human and other complex genomes. We used 19/20-bp genomic DNA tags to localize individual DNase I cutting events in nuclear chromatin and produced approximately 257,000 tags from erythroid cells. Tags were mapped to the human genome, and a quantitative algorithm was applied to discriminate statistically significant clusters of independent DNase I cutting events. We show that such clusters identify both known regulatory sequences and previously unrecognized functional elements across the genome. We used in silico simulation to demonstrate that DACS is capable of efficient and accurate localization of the majority of DNase I-hypersensitive sites in the human genome without requiring an independent validation step. A unique feature of DACS is that it permits unbiased evaluation of the chromatin state of regulatory sequences from widely separated genomic loci. We found surprisingly large differences in the accessibility of distant regulatory sequences, suggesting the existence of a hierarchy of nuclear organization that escapes detection by conventional chromatin assays. 相似文献
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Occupancy of the Drosophila hsp70 promoter by a subset of basal transcription factors diminishes upon transcriptional activation 下载免费PDF全文
Lebedeva LA Nabirochkina EN Kurshakova MM Robert F Krasnov AN Evgen'ev MB Kadonaga JT Georgieva SG Tora L 《Proceedings of the National Academy of Sciences of the United States of America》2005,102(50):18087-18092