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Ekwall, Karl
Publications (10 of 48) Show all publications
Kärblane, K., Gerassimenko, J., Nigul, L., Piirsoo, A., Smialowska, A., Vinkel, K., . . . Sarmiento, C. (2015). ABCE1 Is a Highly Conserved RNA Silencing Suppressor. PLoS ONE, 10(2), Article ID e0116702.
Open this publication in new window or tab >>ABCE1 Is a Highly Conserved RNA Silencing Suppressor
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2015 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 2, article id e0116702Article in journal (Refereed) Published
Abstract [en]

ATP-binding cassette sub-family E member 1 (ABCE1) is a highly conserved protein among eukaryotes and archaea. Recent studies have identified ABCE1 as a ribosome-recycling factor important for translation termination in mammalian cells, yeast and also archaea. Here we report another conserved function of ABCE1. We have previously described AtRLI2, the homolog of ABCE1 in the plant Arabidopsis thaliana, as an endogenous suppressor of RNA silencing. In this study we show that this function is conserved: human ABCE1 is able to suppress RNA silencing in Nicotiana benthamiana plants, in mammalian HEK293 cells and in the worm Caenorhabditis elegans. Using co-immunoprecipitation and mass spectrometry, we found a number of potential ABCE1-interacting proteins that might support its function as an endogenous suppressor of RNA interference. The interactor candidates are associated with epigenetic regulation, transcription, RNA processing and mRNA surveillance. In addition, one of the identified proteins is translin, which together with its binding partner TRAX supports RNA interference.

National Category
Biological Sciences
Identifiers
urn:nbn:se:sh:diva-26400 (URN)10.1371/journal.pone.0116702 (DOI)000349444900060 ()25659154 (PubMedID)2-s2.0-84922720162 (Scopus ID)
Funder
The Foundation for Baltic and East European Studies, 300501
Available from: 2015-02-12 Created: 2015-02-12 Last updated: 2018-07-18Bibliographically approved
Smialowska, A., Djupedal, I., Wang, J., Kylsten, P., Swoboda, P. & Ekwall, K. (2014). RNAi mediates post-transcriptional repression of gene expression in fission yeast Schizosaccharomyces pombe. Biochemical and Biophysical Research Communications - BBRC, 444(2), 254-259
Open this publication in new window or tab >>RNAi mediates post-transcriptional repression of gene expression in fission yeast Schizosaccharomyces pombe
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2014 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 444, no 2, p. 254-259Article in journal (Other academic) Published
Abstract [en]

RNA interference (RNAi) is a gene silencing mechanism conserved from fungi to mammals. Small interfering RNAs are products and mediators of the RNAi pathway and act as specificity factors in recruiting effector complexes. The Schizosaccharomyces pombe genome encodes one of each of the core RNAi proteins, Dicer, Argonaute and RNA-dependent RNA polymerase (dcr1, ago1, rdp1). Even though the function of RNAi in heterochromatin assembly in S. pombe is established, its role in controlling gene expression is elusive. Here, we report the identification of small RNAs mapped anti-sense to protein coding genes in fission yeast. We demonstrate that these genes are up-regulated at the protein level in RNAi mutants, while their mRNA levels are not significantly changed. We show that the repression by RNAi is not a result of heterochromatin formation. Thus, we conclude that RNAi is involved in post-transcriptional gene silencing in S. pombe.

Keywords
Fission yeast, PTGS, RNAi
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:sh:diva-22232 (URN)10.1016/j.bbrc.2014.01.057 (DOI)000331923500025 ()24462781 (PubMedID)2-s2.0-84892926000 (Scopus ID)
Funder
The Foundation for Baltic and East European Studies, 300501Swedish Cancer Society, CAN-2009Swedish Research Council, VR-NT-2007-4722
Available from: 2014-02-14 Created: 2014-02-14 Last updated: 2018-07-20Bibliographically approved
Rhind, N., Chen, Z., Yassour, M., Thompson, D. A., Haas, B. J., Habib, N., . . . Nusbaum, C. (2011). Comparative Functional Genomics of the Fission Yeasts. Science, 332(6032), 930-936
Open this publication in new window or tab >>Comparative Functional Genomics of the Fission Yeasts
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2011 (English)In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 332, no 6032, p. 930-936Article in journal (Refereed) Published
Abstract [en]

The fission yeast clade-comprising Schizosaccharomyces pombe, S. octosporus, S. cryophilus, and S. japonicus-occupies the basal branch of Ascomycete fungi and is an important model of eukaryote biology. A comparative annotation of these genomes identified a near extinction of transposons and the associated innovation of transposon-free centromeres. Expression analysis established that meiotic genes are subject to antisense transcription during vegetative growth, which suggests a mechanism for their tight regulation. In addition, trans-acting regulators control new genes within the context of expanded functional modules for meiosis and stress response. Differences in gene content and regulation also explain why, unlike the budding yeast of Saccharomycotina, fission yeasts cannot use ethanol as a primary carbon source. These analyses elucidate the genome structure and gene regulation of fission yeast and provide tools for investigation across the Schizosaccharomyces clade.

National Category
Biochemistry and Molecular Biology Microbiology
Identifiers
urn:nbn:se:sh:diva-14957 (URN)10.1126/science.1203357 (DOI)000290766600034 ()21511999 (PubMedID)2-s2.0-79956319465 (Scopus ID)
Available from: 2012-01-24 Created: 2012-01-24 Last updated: 2018-07-18Bibliographically approved
Strålfors, A., Walfridsson, J., Bhuiyan, H. & Ekwall, K. (2011). The FUN30 Chromatin Remodeler, Fft3, Protects Centromeric and Subtelomeric Domains from Euchromatin Formation. PLoS Genetics, 7(3), Article ID e1001334.
Open this publication in new window or tab >>The FUN30 Chromatin Remodeler, Fft3, Protects Centromeric and Subtelomeric Domains from Euchromatin Formation
2011 (English)In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 7, no 3, article id e1001334Article in journal (Refereed) Published
Abstract [en]

The chromosomes of eukaryotes are organized into structurally and functionally discrete domains. This implies the presence of insulator elements that separate adjacent domains, allowing them to maintain different chromatin structures. We show that the Fun30 chromatin remodeler, Fft3, is essential for maintaining a proper chromatin structure at centromeres and subtelomeres. Fft3 is localized to insulator elements and inhibits euchromatin assembly in silent chromatin domains. In its absence, euchromatic histone modifications and histone variants invade centromeres and subtelomeres, causing a mis-regulation of gene expression and severe chromosome segregation defects. Our data strongly suggest that Fft3 controls the identity of chromatin domains by protecting these regions from euchromatin assembly.

National Category
Genetics
Identifiers
urn:nbn:se:sh:diva-14962 (URN)10.1371/journal.pgen.1001334 (DOI)000288996600016 ()21437270 (PubMedID)2-s2.0-79953741267 (Scopus ID)
Available from: 2012-01-24 Created: 2012-01-24 Last updated: 2017-07-17Bibliographically approved
Khorosjutina, O., Wanrooij, P. H., Walfridsson, J., Szilagyi, Z., Zhu, X., Baraznenok, V., . . . Gustafsson, C. M. (2010). A Chromatin-remodeling Protein Is a Component of Fission Yeast Mediator. Journal of Biological Chemistry, 285(39), 29729-29737
Open this publication in new window or tab >>A Chromatin-remodeling Protein Is a Component of Fission Yeast Mediator
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2010 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 285, no 39, p. 29729-29737Article in journal (Refereed) Published
Abstract [en]

The multiprotein Mediator complex is an important regulator of RNA polymerase II-dependent genes in eukaryotic cells. In contrast to the situation in many other eukaryotes, the conserved Med15 protein is not a stable component of Mediator isolated from fission yeast. We here demonstrate that Med15 exists in a protein complex together with Hrp1, a CHD1 ATP-dependent chromatin-remodeling protein. The Med15-Hrp1 subcomplex is not a component of the core Mediator complex but can interact with the L-Mediator conformation. Deletion of med15(+) and hrp1(+) causes very similar effects on global steady-state levels of mRNA, and genome-wide analyses demonstrate that Med15 associates with a distinct subset of Hrp1-bound gene promoters. Our findings therefore indicate that Mediator may directly influence histone density at regulated promoters.

National Category
Biological Sciences
Identifiers
urn:nbn:se:sh:diva-13969 (URN)10.1074/jbc.M110.153858 (DOI)000281984300008 ()2-s2.0-77956924896 (Scopus ID)
Available from: 2011-12-16 Created: 2011-12-15 Last updated: 2017-12-08Bibliographically approved
Persson, J. & Ekwall, K. (2010). Chd1 remodelers maintain open chromatin and regulate the epigenetics of differentiation. Experimental Cell Research, 316(8), 1316-1323
Open this publication in new window or tab >>Chd1 remodelers maintain open chromatin and regulate the epigenetics of differentiation
2010 (English)In: Experimental Cell Research, ISSN 0014-4827, E-ISSN 1090-2422, Vol. 316, no 8, p. 1316-1323Article in journal (Refereed) Published
Abstract [en]

Eukaryotic DNA is packaged around octamers of histone proteins into nucleosomes, the basic unit of chromatin. In addition to enabling meters of DNA to fit within the confines of a nucleus, the structure of chromatin has functional implications for cell identity. Covalent chemical modifications to the DNA and to histones, histone variants, ATP-dependent chromatin remodelers, small noncoding RNAs and the level of chromatin compaction all contribute to chromosomal structure and to the activity or silencing of genes. These chromatin-level alterations are defined as epigenetic when they are heritable from mother to daughter cell. The great diversity of epigenomes that can arise from a single genome permits a single, totipotent cell to generate the hundreds of distinct cell types found in humans. Two recent studies in mouse and in fly have highlighted the importance of Chd1 chromatin remodelers for maintaining an open, active chromatin state. Based on evidence from fission yeast as a model system, we speculate that Chd1 remodelers are involved in the disassembly of nucleosomes at promoter regions, thus promoting active transcription and open chromatin. It is likely that these nucleosomes are specifically marked for disassembly by the histone variant H2A.Z.

Keywords
Chd1, Chromatin, Development, Epigenetics, adenosine triphosphate, cell protein, DNA, histone, histone H2AZ, protein Chd1, unclassified drug, untranslated RNA, CHD1 protein, human, Chd1 protein, mouse, DNA binding protein, helicase, cell differentiation, cell nucleus, cell type, chemical modification, chromosome structure, daughter cell, Drosophila melanogaster, gene silencing, genome, human, nonhuman, nucleosome, priority journal, regulatory mechanism, review, Saccharomyces cerevisiae, stem cell, animal, chromatin assembly and disassembly, genetic epigenesis, physiology, Eukaryota, Schizosaccharomycetaceae, Animals, DNA Helicases, DNA-Binding Proteins, Epigenesis, Genetic, Humans
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:sh:diva-20809 (URN)10.1016/j.yexcr.2010.02.029 (DOI)000277817800007 ()20211173 (PubMedID)2-s2.0-77952570482 (Scopus ID)
Available from: 2013-12-18 Created: 2013-12-18 Last updated: 2017-12-06Bibliographically approved
Hogan, C. J., Aligianni, S., Durand-Dubief, M., Persson, J., Will, W. R., Webster, J., . . . Varga-Weisz, P. D. (2010). Fission yeast Iec1-Ino80-mediated nucleosome eviction regulates nucleotide and phosphate metabolism. Molecular and Cellular Biology, 30(3), 657-674
Open this publication in new window or tab >>Fission yeast Iec1-Ino80-mediated nucleosome eviction regulates nucleotide and phosphate metabolism
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2010 (English)In: Molecular and Cellular Biology, ISSN 0270-7306, E-ISSN 1098-5549, Vol. 30, no 3, p. 657-674Article in journal (Refereed) Published
Abstract [en]

Ino80 is an ATP-dependent nucleosome-remodeling enzyme involved in transcription, replication, and the DNA damage response. Here, we characterize the fission yeast Ino80 and find that it is essential for cell viability. We show that the Ino80 complex from fission yeast mediates ATP-dependent nucleosome remodeling in vitro. The purification of the Ino80-associated complex identified a highly conserved complex and the presence of a novel zinc finger protein with similarities to the mammalian transcriptional regulator Yin Yang 1 (YY1) and other members of the GLI-Krüppel family of proteins. Deletion of this Iec1 protein or the Ino80 complex subunit arp8, ies6, or ies2 causes defects in DNA damage repair, the response to replication stress, and nucleotide metabolism. We show that Iec1 is important for the correct expression of genes involved in nucleotide metabolism, including the ribonucleotide reductase subunit cdc22 and phosphate- and adenineresponsive genes. We find that Ino80 is recruited to a large number of promoter regions on phosphate starvation, including those of phosphate- and adenine-responsive genes that depend on Iec1 for correct expression. Iec1 is required for the binding of Ino80 to target genes and subsequent histone loss at the promoter and throughout the body of these genes on phosphate starvation. This suggests that the Iec1-Ino80 complex promotes transcription through nucleosome eviction.

Keywords
adenine, nucleotide, phosphate, protein kinase, protein subunit, ribonucleotide reductase, transcription factor YY1, zinc finger protein, article, cell viability, DNA damage, DNA repair, DNA replication, gene targeting, nonhuman, nucleosome, nucleotide metabolism, phosphate metabolism, priority journal, promoter region, protein binding, protein purification, transcription regulation, yeast, Amino Acid Sequence, Cell Cycle Proteins, Gene Expression Regulation, Fungal, Microarray Analysis, Molecular Sequence Data, Nucleosomes, Nucleotides, Phosphates, Schizosaccharomyces, Schizosaccharomyces pombe Proteins, Transcription Factors, Zinc Fingers, Mammalia, Schizosaccharomycetaceae
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:sh:diva-20793 (URN)10.1128/MCB.01117-09 (DOI)000273700700009 ()19933844 (PubMedID)2-s2.0-75149118600 (Scopus ID)
Available from: 2013-12-18 Created: 2013-12-18 Last updated: 2017-07-18Bibliographically approved
Sinha, I., Buchanan, L., Rönnerblad, M., Bonilla, C., Durand-Dubief, M., Shevchenko, A., . . . Ekwall, K. (2010). Genome-wide mapping of histone modifications and mass spectrometry reveal H4 acetylation bias and H3K36 methylation at gene promoters in fission yeast. Epigenomics, 2(3), 377-393
Open this publication in new window or tab >>Genome-wide mapping of histone modifications and mass spectrometry reveal H4 acetylation bias and H3K36 methylation at gene promoters in fission yeast
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2010 (English)In: Epigenomics, ISSN 1750-1911, Vol. 2, no 3, p. 377-393Article in journal (Refereed) Published
Abstract [en]

To map histone modifications with unprecedented resolution both globally and locus-specifically, and to link modification patterns to gene expression. Materials & methods: Using correlations between quantitative mass spectrometry and chromatin immunoprecipitation/microarray analyses, we have mapped histone post-translational modifications in fission yeast (Schizosaccharomyces pombe). Results: Acetylations at lysine 9, 18 and 27 of histone H3 give the best positive correlations with gene expression in this organism. Using clustering analysis and gene ontology search tools, we identified promoter histone modification patterns that characterize several classes of gene function. For example, gene promoters of genes involved in cytokinesis have high H3K36me2 and low H3K4me2, whereas the converse pattern is found ar promoters of gene involved in positive regulation of the cell cycle. We detected acetylation of H4 preferentially at lysine 16 followed by lysine 12, 8 and 5. Our analysis shows that this H4 acetylation bias in the coding regions is dependent upon gene length and linked to gene expression. Our analysis also reveals a role for H3K36 methylation at gene promoters where it functions in a crosstalk between the histone methyltransferase Set2(KMT3) and the histone deacetylase Clr6, which removes H3K27ac leading to repression of transcription. Conclusion: Histone modification patterns could be linked to gene expression in fission yeast.

National Category
Biological Sciences
Identifiers
urn:nbn:se:sh:diva-13987 (URN)10.2217/EPI.10.18 (DOI)000278533000009 ()2-s2.0-77954091620 (Scopus ID)
Note

Som manuskript i avhandling. As manuscript in dissertation.

Available from: 2011-12-16 Created: 2011-12-15 Last updated: 2017-12-08Bibliographically approved
Djupedal, I., Kos-Braun, I. C., Mosher, R. A., Söderholm, N., Simmer, F., Hardcastle, T. J., . . . Ekwall, K. (2009). Analysis of small RNA in fission yeast; centromeric siRNAs are potentially generated through a structured RNA. EMBO Journal, 28(24), 3832-3844
Open this publication in new window or tab >>Analysis of small RNA in fission yeast; centromeric siRNAs are potentially generated through a structured RNA
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2009 (English)In: EMBO Journal, ISSN 0261-4189, E-ISSN 1460-2075, Vol. 28, no 24, p. 3832-3844Article in journal (Refereed) Published
Abstract [en]

The formation of heterochromatin at the centromeres in fission yeast depends on transcription of the outer repeats. These transcripts are processed into siRNAs that target homologous loci for heterochromatin formation. Here, high throughput sequencing of small RNA provides a comprehensive analysis of centromere-derived small RNAs. We found that the centromeric small RNAs are Dcr1 dependent, carry 50-monophosphates and are associated with Ago1. The majority of centromeric small RNAs originate from two remarkably well-conserved sequences that are present in all centromeres. The high degree of similarity suggests that this non-coding sequence in itself may be of importance. Consistent with this, secondary structure-probing experiments indicate that this centromeric RNA is partially double-stranded and is processed by Dicer in vitro. We further demonstrate the existence of small centromeric RNA in rdp1D cells. Our data suggest a pathway for siRNA generation that is distinct from the well-documented model involving RITS/RDRC. We propose that primary transcripts fold into hairpin-like structures that may be processed by Dcr1 into siRNAs, and that these siRNAs may initiate heterochromatin formation independent of RDRC activity. The EMBO Journal (2009) 28, 3832-3844. doi: 10.1038/emboj.2009.351; Published online 26 November 2009

Keywords
centromeres, RNAi, small RNA, S. pombe
National Category
Biochemistry and Molecular Biology Cell Biology
Identifiers
urn:nbn:se:sh:diva-17674 (URN)10.1038/emboj.2009.351 (DOI)000272833700006 ()19942857 (PubMedID)2-s2.0-72449159549 (Scopus ID)
Funder
Swedish Cancer SocietySwedish Research CouncilEU, European Research Council, LSHGCT-2004-503433
Note

Som manuskript i avhandling. As manuscript in dissertation.

Available from: 2012-12-14 Created: 2012-12-14 Last updated: 2017-07-18Bibliographically approved
Djupedal, I. & Ekwall, K. (2009). Epigenetics: heterochromatin meets RNAi. Cell Research, 19(3), 282-295
Open this publication in new window or tab >>Epigenetics: heterochromatin meets RNAi
2009 (English)In: Cell Research, ISSN 1001-0602, E-ISSN 1748-7838, Vol. 19, no 3, p. 282-295Article in journal (Refereed) Published
Abstract [en]

The term epigenetics refers to heritable changes not encoded by DNA. The organization of DNA into chromatin fibers affects gene expression in a heritable manner and is therefore one mechanism of epigenetic inheritance. Large parts of eukaryotic genomes consist of constitutively highly condensed heterochromatin, important for maintaining genome integrity but also for silencing of genes within. Small RNA, together with factors typically associated with RNA interference (RNAi) targets homologous DNA sequences and recruits factors that modify the chromatin, commonly resulting in formation of heterochromatin and silencing of target genes. The scope of this review is to provide an overview of the roles of small RNA and the RNAi components, Dicer, Argonaute and RNA dependent polymerases in epigenetic inheritance via heterochromatin formation, exemplified with pathways from unicellular eukaryotes, plants and animals.

National Category
Cell Biology
Identifiers
urn:nbn:se:sh:diva-13917 (URN)10.1038/cr.2009.13 (DOI)000265700000004 ()19188930 (PubMedID)2-s2.0-61849125304 (Scopus ID)
Available from: 2011-12-14 Created: 2011-12-14 Last updated: 2017-12-08Bibliographically approved
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