| 1. |
- Misulovin, Ziva, et al.
(författare)
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Association of cohesin and Nipped-B with transcriptionally active regions of the Drosophila melanogaster genome
- 2008
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Ingår i: Chromosoma. - : Springer Science and Business Media LLC. - 0009-5915 .- 1432-0886. ; 117:1, s. 89-102
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Tidskriftsartikel (refereegranskat)abstract
- The cohesin complex is a chromosomal component required for sister chromatid cohesion that is conserved from yeast to man. The similarly conserved Nipped-B protein is needed for cohesin to bind to chromosomes. In higher organisms, Nipped-B and cohesin regulate gene expression and development by unknown mechanisms. Using chromatin immunoprecipitation, we find that Nipped-B and cohesin bind to the same sites throughout the entire non-repetitive Drosophila genome. They preferentially bind transcribed regions and overlap with RNA polymerase II. This contrasts sharply with yeast, where cohesin binds almost exclusively between genes. Differences in cohesin and Nipped-B binding between Drosophila cell lines often correlate with differences in gene expression. For example, cohesin and Nipped-B bind the Abd-B homeobox gene in cells in which it is transcribed, but not in cells in which it is silenced. They bind to the Abd-B transcription unit and downstream regulatory region and thus could regulate both transcriptional elongation and activation. We posit that transcription facilitates cohesin binding, perhaps by unfolding chromatin, and that Nipped-B then regulates gene expression by controlling cohesin dynamics. These mechanisms are likely involved in the etiology of Cornelia de Lange syndrome, in which mutation of one copy of the NIPBL gene encoding the human Nipped-B ortholog causes diverse structural and mental birth defects.
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| 2. |
- Berkaeva, Maria, et al.
(författare)
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Functional analysis of Drosophila polytene chromosomes decompacted unit: the interband
- 2009
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Ingår i: Chromosome Research. - : Springer Science and Business Media LLC. - 0967-3849 .- 1573-6849. ; 17:6, s. 745-754
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Tidskriftsartikel (refereegranskat)abstract
- Differential compaction of the interphase chromosomes is important for proper functioning of the eukaryotic genome. Such non-uniform compaction is most easily observed in Drosophila salivary gland polytene chromosomes as a reproducible banding pattern. Functional mechanisms underlying the establishment and maintenance of the banding pattern remain unclear but have been hypothesized to involve transcription and chromatin insulators. We tested functional properties of DNA fragments from several transcriptionally inert interband regions that behave as autonomous decompacted units of polytene chromosomes. Our results suggest that, in the absence of transcription, the decondensed state of interband regions does not depend on the presence of insulator elements but instead correlates with the presence of transcriptional enhancers.
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| 3. |
- Hasegawa, H., et al.
(författare)
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Kelvin-Helmholtz waves at the Earth's magnetopause : Multiscale development and associated reconnection
- 2009
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Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 114:12, s. A12207-
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Tidskriftsartikel (refereegranskat)abstract
- We examine traversals on 20 November 2001 of the equatorial magnetopause boundary layer simultaneously at similar to 1500 magnetic local time (MLT) by the Geotail spacecraft and at similar to 1900 MLT by the Cluster spacecraft, which detected rolled-up MHD-scale vortices generated by the Kelvin-Helmholtz instability (KHI) under prolonged northward interplanetary magnetic field conditions. Our purpose is to address the excitation process of the KHI, MHD-scale and ion-scale structures of the vortices, and the formation mechanism of the low-latitude boundary layer (LLBL). The observed KH wavelength (>4 x 10(4) km) is considerably longer than predicted by the linear theory from the thickness (similar to 1000 km) of the dayside velocity shear layer. Our analyses suggest that the KHI excitation is facilitated by combined effects of the formation of the LLBL presumably through high-latitude magnetopause reconnection and compressional magnetosheath fluctuations on the dayside, and that breakup and/or coalescence of the vortices are beginning around 1900 MLT. Current layers of thickness a few times ion inertia length similar to 100 km and of magnetic shear similar to 60 degrees existed at the trailing edges of the vortices. Identified in one such current sheet were signatures of local reconnection: Alfvenic outflow jet within a bifurcated current sheet, nonzero magnetic field component normal to the sheet, and field-aligned beam of accelerated electrons. Because of its incipient nature, however, this reconnection process is unlikely to lead to the observed dusk-flank LLBL. It is thus inferred that the flank LLBL resulted from other mechanisms, namely, diffusion and/or remote reconnection unidentified by Cluster.
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| 4. |
- Kahn, Tatyana G, et al.
(författare)
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Polycomb complexes and the propagation of the methylation mark at the Drosophila ubx gene
- 2006
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 281:39, s. 29064-29075
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Tidskriftsartikel (refereegranskat)abstract
- Polycomb group proteins are transcriptional repressors that control many developmental genes. The Polycomb group protein Enhancer of Zeste has been shown in vitro to methylate specifically lysine 27 and lysine 9 of histone H3 but the role of this modification in Polycomb silencing is unknown. We show that H3 trimethylated at lysine 27 is found on the entire Ubx gene silenced by Polycomb. However, Enhancer of Zeste and other Polycomb group proteins stay primarily localized at their response elements, which appear to be the least methylated parts of the silenced gene. Our results suggest that, contrary to the prevailing view, the Polycomb group proteins and methyltransferase complexes are recruited to the Polycomb response elements independently of histone methylation and then loop over to scan the entire region, methylating all accessible nucleosomes. We propose that the Polycomb chromodomain is required for the looping mechanism that spreads methylation over a broad domain, which in turn is required for the stability of the Polycomb group protein complex. Both the spread of methylation from the Polycomb response elements, and the silencing effect can be blocked by the gypsy insulator.
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| 5. |
- Schaaf, Cheri A, et al.
(författare)
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Regulation of the Drosophila Enhancer of split and invected-engrailed gene complexes by sister chromatid cohesion proteins
- 2009
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 4:7, s. e6202-
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Tidskriftsartikel (refereegranskat)abstract
- The cohesin protein complex was first recognized for holding sister chromatids together and ensuring proper chromosome segregation. Cohesin also regulates gene expression, but the mechanisms are unknown. Cohesin associates preferentially with active genes, and is generally absent from regions in which histone H3 is methylated by the Enhancer of zeste [E(z)] Polycomb group silencing protein. Here we show that transcription is hypersensitive to cohesin levels in two exceptional cases where cohesin and the E(z)-mediated histone methylation simultaneously coat the entire Enhancer of split and invected-engrailed gene complexes in cells derived from Drosophila central nervous system. These gene complexes are modestly transcribed, and produce seven of the twelve transcripts that increase the most with cohesin knockdown genome-wide. Cohesin mutations alter eye development in the same manner as increased Enhancer of split activity, suggesting that similar regulation occurs in vivo. We propose that cohesin helps restrain transcription of these gene complexes, and that deregulation of similarly cohesin-hypersensitive genes may underlie developmental deficits in Cornelia de Lange syndrome.
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| 6. |
- Schwartz, Yuri B, et al.
(författare)
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A little bit of sugar makes polycomb better
- 2009
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Ingår i: Journal of molecular cell biology. - : Oxford University Press (OUP). - 1759-4685 .- 1674-2788. ; 1:1, s. 11-12
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Tidskriftsartikel (refereegranskat)abstract
- Transcriptional repression by Polycomb group (PcG) proteins is now sweetened by the discovery of the essential role of O-GlcNAc glycosylation in the process. PcG protein polyhomeotic may be the key target, but alternative or additional functions including repression of transcription through glycosylation of the C-terminal domain of RNA polymerase II are also possible.
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| 7. |
- Schwartz, Yuri B, et al.
(författare)
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Characteristic low density and shear sensitivity of cross-linked chromatin containing polycomb complexes
- 2005
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Ingår i: Molecular and Cellular Biology. - 0270-7306 .- 1098-5549. ; 25:1, s. 432-439
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Tidskriftsartikel (refereegranskat)abstract
- Chromatin cross-linking is widely used for mapping the distribution of chromosomal proteins by immunoprecipitation, but our knowledge of the physical properties of chromatin complexes remains rudimentary. Density gradients have been long used to separate fragments of cross-linked chromatin with their bound proteins from free protein or free DNA. We find that the association of DNA fragments with very-high-molecular-weight protein complexes shifts their buoyant density to values much lower then that of bulk chromatin. We show that in a CsCl gradient, Polycomb response elements, promoters of active genes, and insulator or boundary elements are found at buoyant densities similar to those of free protein and are depleted from the bulk chromatin fractions. In these regions, the low density is associated with the presence of large protein complexes and with high sensitivity to sonication. Our results suggest that separation of different chromatin regions according to their buoyant density may bias chromatin immunoprecipitation results. Density centrifugation of cross-linked chromatin may provide a simple approach to investigate the properties of large chromatin complexes in vivo.
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| 8. |
- Schwartz, Yuri B, et al.
(författare)
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Genome-wide analysis of Polycomb targets in Drosophila melanogaster
- 2006
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 38:6, s. 700-705
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Tidskriftsartikel (refereegranskat)abstract
- Polycomb group (PcG) complexes are multiprotein assemblages that bind to chromatin and establish chromatin states leading to epigenetic silencing. PcG proteins regulate homeotic genes in flies and vertebrates, but little is known about other PcG targets and the role of the PcG in development, differentiation and disease. Here, we determined the distribution of the PcG proteins PC, E(Z) and PSC and of trimethylation of histone H3 Lys27 (me3K27) in the D. melanogaster genome. At more than 200 PcG target genes, binding sites for the three PcG proteins colocalize to presumptive Polycomb response elements (PREs). In contrast, H3 me3K27 forms broad domains including the entire transcription unit and regulatory regions. PcG targets are highly enriched in genes encoding transcription factors, but they also include genes coding for receptors, signaling proteins, morphogens and regulators representing all major developmental pathways.
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| 9. |
- Schwartz, Yuri B, et al.
(författare)
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Polycomb complexes and epigenetic states
- 2008
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Ingår i: Current Opinion in Cell Biology. - : Elsevier BV. - 0955-0674 .- 1879-0410. ; 20:3, s. 266-273
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Tidskriftsartikel (refereegranskat)abstract
- Important advances in the study of Polycomb Group (PcG) complexes in the past two years have focused on the role of this repressive system in programing the genome. Genome-wide analyses have shown that PcG mechanisms control a large number of genes regulating many cellular functions and all developmental pathways. Current evidence shows that, contrary to the classical picture of their role, PcG complexes do not set a repressed chromatin state that is maintained throughout development but have a much more dynamic role. PcG target genes can become repressed or be reactivated or exist in intermediate states. What controls the balance between repression and derepression is a crucial question in understanding development and differentiation in higher organisms.
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| 10. |
- Schwartz, Yuri B, et al.
(författare)
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Polycomb silencing mechanisms and the management of genomic programmes
- 2007
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Ingår i: Nature reviews genetics. - : Springer Science and Business Media LLC. - 1471-0056 .- 1471-0064. ; 8:1, s. 9-22
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Tidskriftsartikel (refereegranskat)abstract
- Polycomb group complexes, which are known to regulate homeotic genes, have now been found to control hundreds of other genes in mammals and insects. First believed to progressively assemble and package chromatin, they are now thought to be localized, but induce a methylation mark on histone H3 over a broad chromatin domain. Recent progress has changed our view of how these complexes are recruited, and how they affect chromatin and repress gene activity. Polycomb complexes function as global enforcers of epigenetically repressed states, balanced by an antagonistic state that is mediated by Trithorax. These epigenetic states must be reprogrammed when cells become committed to differentiation.
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