Ragnhild Eskeland

Williamson I, Berlivet S, Eskeland R, Boyle S, Illingworth RS, Paquette D, Dostie J, Bickmore WA. Spatial genome organization: contrasting views from chromosome conformation capture and fluorescence in situ hybridization. Genes Dev. 2014 Dec 15;28(24):2778-91. doi: 10.1101/gad.251694.114.

Taylor G, Eskeland R, Hekimoglu-Balkan B, Pradeepa M, Bickmore WA. H4K16 acetylation marks active genes and enhancers of embryonic stem cells, but does not alter chromatin compaction. Genome Res. 2013 Dec;23(12):2053-65. doi: 10.1101/gr.155028.113. Epub 2013 Aug 29.

Lund E, Oldenburg A, Delbarre E, Freberg C, Duband-Goulet I, Eskeland R, Buendia B, Collas P. Lamin A/C-promoter interactions specify chromatin state-dependent transcription outcomes. Genome Res. 2013 Oct;23(10):1580-9. doi: 10.1101/gr.159400.113. Epub 2013 Jul 16.

D. Greiner, T. Bonaldi, R. Eskeland, E. Roemer and A. Imhof (2013). Reply to "Chaetocin is a nonspecific inhibitor of histone lysine methyltransferases". Nature Chemical Biology. Feb 15;9(3):137.

Williamson I, Eskeland R, Lettice LA, Hill AE, Boyle S, Grimes GR, Hill RE, Bickmore WA (2012). Anterior-posterior differences in HoxD chromatin topology in limb development. Development Sep;139(17):3157-67.

di Pietro M, Lao-Sirieix P, Boyle S, Cassidy A, Castillo D, Saadi A, Eskeland R, Fitzgerald RC. Evidence for a functional role of epigenetically regulated midcluster HOXB genes in the development of Barrett esophagus. Proc Natl Acad Sci U S A. 2012 May 17. [Epub ahead of print]

Illingworth RS, Botting CH, Grimes GR, Bickmore WA*, Eskeland R* (2012). PRC1 and PRC2 are not required for targeting of H2A.Z to developmental genes in embryonic stem cells. PLoS One. 2012;7(4):e34848. Epub 2012 Apr 9. * Co-corresponding authors

Endoh M; Endo T. A.; Endoh T; Isono K; Sharif J; Ohara O; Toyoda T; Ito T; Eskeland R; Bickmore W. A.; Vidal M; Bernstein B. E.; Koseki H. Histone H2A mono-ubiquitination is a crucial step to mediate PRC1-dependent repression of developmental genes to maintain ES cell identity. (2012). PLoS Genetics. 8(7):e1002774.

R. Eskeland, E. Freyer, M. Leeb, A. Wutz, W.A. Bickmore (2011). Histone Acetylation and the Maintenance of Chromatin Compaction by Polycomb Repressive Complexes. Cold Spring Harb Symp Quant Biol. 2010;75:71-8. 

R. Eskeland, M. Leeb, G. Grimes, C. Kress, S. Boyle, D. Sproul, N. Gilbert, Y. Fan, A. I. Skoultchi, A. Wutz and W. A. Bickmore (2010). Ring1B compact chromatin structure and represses gene expression independent of histone ubiquitination. Mol Cell. 38(3):452-64.

M. Lavigne, R. Eskeland, S. Azebi, H. Fan, B. Bourachot, R. E. Kingston, A. Imhof and C. Muchardt (2009). Interaction of HP1 and Brg1/Brm with the globular domain of histone H3 is required for HP1-mediated repression. PLoS Genet.  .Dec;5(12):e1000769

J. Abel, R. Eskeland, G. D. Raffa, E. Kremmer, A. Imhof (2009). Drosophila HP1c is regulated by an auto-regulatory feed back loop through its binding partner Woc. PLoS One. 4(4):e5089.

R. Eskeland, A. Eberharter and A. Imhof (2007). HP1 binding to chromatin methylated at H3K9 is enhanced by auxiliary factors. Molecular and Cellular Biology, 27(2):453-65.

M. Stabell, R. Eskeland, M. Bjørkmo, J. Larson, R. B. Aalen, A. Imhof and A. Lambertson (2006). The Drosophila G9a gene encodes a multicatalytic histone methyltransferase required for normal development. Nucleic Acids Research, 34(16):4609-21

D. Greiner, T. Bonaldi, R. Eskeland, E. Roemer and A. Imhof (2005). Identification of a specific inhibitor of the histone methyltransferase SU(VAR)3-9. Nature Chemical Biology, 1:143-5

R. Eskeland#, B. Czermin#, J. Boeke, T. Bonaldi, J. T. Regula, and A. Imhof (2004). The N-terminus of Drosophila SU(VAR)3-9 mediates dimerization and regulates its methyltransferase activity. Biochemistry, 43(12):3740-9. # These authors contributed equally 

• Lemma, Roza Berhanu; Ledsaak, Marit; Fuglerud, Bettina Maria; Sandve, Geir Kjetil; Eskeland, Ragnhild & Gabrielsen, Odd Stokke (2021). Chromatin occupancy and target genes of the haematopoietic master transcription factor MYB. Scientific Reports.  ISSN 2045-2322.  11(9008) . doi: 10.1038/s41598-021-88516-w Show summary

  The transcription factor MYB is a master regulator in haematopoietic progenitor cells and a pioneer factor affecting differentiation and proliferation of these cells. Leukaemic transformation may be promoted by high MYB levels. Despite much accumulated molecular knowledge of MYB, we still lack a comprehensive understanding of its target genes and its chromatin action. In the present work, we performed a ChIP-seq analysis of MYB in K562 cells accompanied by detailed bioinformatics analyses. We found that MYB occupies both promoters and enhancers. Five clusters (C1–C5) were found when we classified MYB peaks according to epigenetic profiles. C1 was enriched for promoters and C2 dominated by enhancers. C2-linked genes were connected to hematopoietic specific functions and had GATA factor motifs as second in frequency. C1 had in addition to MYB-motifs a significant frequency of ETS-related motifs. Combining ChIP-seq data with RNA-seq data allowed us to identify direct MYB target genes. We also compared ChIP-seq data with digital genomic footprinting. MYB is occupying nearly a third of the super-enhancers in K562. Finally, we concluded that MYB cooperates with a subset of the other highly expressed TFs in this cell line, as expected for a master regulator

• Fuglerud, Bettina Maria; Ledsaak, Marit; Rogne, Marie; Eskeland, Ragnhild & Gabrielsen, Odd Stokke (2018). The pioneer factor activity of c-Myb involves recruitment of p300 and induction of histone acetylation followed by acetylation-induced chromatin dissociation. Epigenetics & Chromatin.  ISSN 1756-8935.  11(1) . doi: 10.1186/s13072-018-0208-y Full text in Research Archive.
• Rodriguez- Castañeda, Fernando; Lemma, Roza Berhanu; Cuervo Torre, Ignacio; Bengtsen, Mads; Moen, Lisa Marie; Ledsaak, Marit; Eskeland, Ragnhild & Gabrielsen, Odd Stokke (2018). The SUMO protease SENP1 and the chromatin remodeller CHD3 interact and jointly affect chromatin accessibility and gene expression. Journal of Biological Chemistry.  ISSN 0021-9258.  293(40), s 15439- 15454 . doi: 10.1074/jbc.RA118.002844 Full text in Research Archive. Show summary

  The small ubiquitin-like modifier (SUMO) post-translationally modifies lysine residues of transcription factors and co-regulators and thereby contributes to an important layer of control of the activities of these transcriptional regulators. Likewise, deSUMOylation of these factors by the sentrin-specific proteases (SENPs) also plays a role in gene regulation, but whether SENPs functionally interact with other regulatory factors that control gene expression is unclear. In the present work, we focused on SENP1, specifically, on its role in activation of gene expression investigated through analysis of the SENP1 interactome, which revealed that SENP1 physically interacts with the chromatin remodeler chromodomain helicase DNA-binding protein 3 (CHD3). Using several additional methods, including GST pull-down and co-immunoprecipitation assays, we validated and mapped this interaction, and using CRISPR-Cas9–generated CHD3- and SENP1-KO cells (in the haploid HAP1 cell line), we investigated whether these two proteins are functionally linked in regulating chromatin remodeling and gene expression. Genome-wide ATAC-Seq analysis of the CHD3- and SENP1-KO cells revealed a large degree of overlap in differential chromatin openness between these two mutant cell lines. Moreover, motif analysis and comparison with ChIP-Seq profiles in K562 cells pointed to an association of CHD3 and SENP1 with CCCTC-binding factor (CTCF) and SUMOylated chromatin–associated factors. Lastly, genome-wide RNA-Seq also indicated that these two proteins co-regulate the expression of several genes. We propose that the functional link between chromatin remodeling by CHD3 and deSUMOylation by SENP1 uncovered here provides another level of control of gene expression.

• Fleischer, Thomas; Tekpli, Xavier; Mathelier, Anthony; Wang, Shixiong; Nebdal, Daniel J.H.; Dhakal, Hari Prasad; Sahlberg, Kristine Kleivi; Schlichting, Ellen; Børresen-Dale, Anne-Lise; Borgen, Elin; Naume, Bjørn; Eskeland, Ragnhild; Frigessi, Arnoldo; Tost, Jörg; Rodriguez, Antoni Hurtado & Kristensen, Vessela N. (2017). DNA methylation at enhancers identifies distinct breast cancer lineages. Nature Communications.  ISSN 2041-1723.  8(1379) . doi: 10.1038/s41467-017-00510-x Full text in Research Archive.
• Fuglerud, Bettina Maria; Lemma, Roza Berhanu; Wanichawan, Pimthanya; Sundaram, Arvind; Eskeland, Ragnhild & Gabrielsen, Odd Stokke (2017). A c-Myb mutant causes deregulated differentiation due to impaired histone binding and abrogated pioneer factor function. Nucleic Acids Research (NAR).  ISSN 0305-1048.  45(13), s 7681- 7696 . doi: 10.1093/nar/gkx364 Full text in Research Archive.
• Gervin, Kristina; Nordeng, Hedvig Marie Egeland; Eskeland, Ragnhild; Paulsen, Ragnhild Elisabeth & Lyle, Robert (2017). Farmakoepigenetikk: Samspillet mellom legemidler og epigenetikk. Norsk Farmaceutisk Tidsskrift.  ISSN 0029-1935.  125(8), s 30- 34 Full text in Research Archive.
• Maclennan, Marie; García-Cañadas, Marta; Reichmann, Judith; Khazina, Elena; Wagner, Gabriele; Playfoot, Christopher J.; Salvador-Palomeque, Carmen; Mann, Abigail R.; Peressini, Paula; Sanchez, Laura; Dobie, Karen; Read, David; Hung, Chao-Chun; Eskeland, Ragnhild; Meehan, Richard R.; Weichenrieder, Oliver; García-Pérez, Jose Luis & Adams, Ian R. (2017). Mobilization of LINE-1 retrotransposons is restricted by Tex19.1 in mouse embryonic stem cells. eLIFE.  ISSN 2050-084X.  6:e26152, s 1- 32 . doi: 10.7554/eLife.26152 Full text in Research Archive.
• Simovski, Boris; Vodak, Daniel; Gundersen, Sveinung; Domanska, Diana Ewa; Azab, Abdulrahman; Holden, Lars; Holden, Marit; Grytten, Ivar; Rand, Knut Dagestad; Drabløs, Finn; Johansen, Morten; Mora Ortiz, Antonio Carlos; Lund-Andersen, Christin; Fromm, Bastian; Eskeland, Ragnhild; Gabrielsen, Odd Stokke; Ferkingstad, Egil; Nakken, Sigve; Bengtsen, Mads; Nederbragt, Alexander Johan; Thorarensen, Hildur Sif; Akse, Johannes Andreas; Glad, Ingrid Kristine; Hovig, Johannes Eivind & Sandve, Geir Kjetil (2017). GSuite HyperBrowser: integrative analysis of dataset collections across the genome and epigenome. GigaScience.  ISSN 2047-217X.  6(7), s 1- 12 . doi: 10.1093/gigascience/gix032 Full text in Research Archive. Show summary

  Background: Recent large-scale undertakings such as ENCODE and Roadmap Epigenomics have generated experimental data mapped to the human reference genome (as genomic tracks) representing a variety of functional elements across a large number of cell types. Despite the high potential value of these publicly available data for a broad variety of investigations, little attention has been given to the analytical methodology necessary for their widespread utilisation. Findings: We here present a first principled treatment of the analysis of collections of genomic tracks. We have developed novel computational and statistical methodology to permit comparative and confirmatory analyses across multiple and disparate data sources. We delineate a set of generic questions that are useful across a broad range of investigations and discuss the implications of choosing different statistical measures and null models. Examples include contrasting analyses across different tissues or diseases. The methodology has been implemented in a comprehensive open-source software system, the GSuite HyperBrowser. To make the functionality accessible to biologists, and to facilitate reproducible analysis, we have also developed a web-based interface providing an expertly guided and customizable way of utilizing the methodology. With this system, many novel biological questions can flexibly be posed and rapidly answered. Conclusions: Through a combination of streamlined data acquisition, interoperable representation of dataset collections and customizable statistical analysis with guided setup and interpretation, the GSuite HyperBrowser represents a first comprehensive solution for integrative analysis of track collections across the genome and epigenome. The software is available at: https://hyperbrowser.uio.no

• Ledsaak, Marit; Bengtsen, Mads; Molværsmyr, Ann-Kristin; Fuglerud, Bettina Maria; Matre, Vilborg; Eskeland, Ragnhild & Gabrielsen, Odd Stokke (2016). PIAS1 binds p300 and behaves as a coactivator or corepressor of the transcription factor c-Myb dependent on SUMO-status. Biochimica et Biophysica Acta. Gene Regulatory Mechanisms.  ISSN 1874-9399.  1859(5), s 705- 718 . doi: 10.1016/j.bbagrm.2016.03.011
• Bengtsen, Mads; Klepper, Kjetil; Gundersen, Sveinung; Cuervo Torre, Ignacio; Drabløs, Finn; Hovig, Johannes Eivind; Sandve, Geir Kjetil F.; Gabrielsen, Odd Stokke & Eskeland, Ragnhild (2015). c-Myb Binding Sites in Haematopoietic Chromatin Landscapes. PLOS ONE.  ISSN 1932-6203.  10(7) . doi: 10.1371/journal.pone.0133280 Full text in Research Archive. Show summary

  Strict control of tissue-specific gene expression plays a pivotal role during lineage commit- ment. The transcription factor c-Myb has an essential role in adult haematopoiesis and func- tions as an oncogene when rearranged in human cancers. Here we have exploited digital genomic footprinting analysis to obtain a global picture of c-Myb occupancy in the genome of six different haematopoietic cell-types. We have biologically validated several c-Myb foot- prints using c-Myb knockdown data, reporter assays and DamID analysis. We show that our predicted conserved c-Myb footprints are highly dependent on the haematopoietic cell type, but that there is a group of gene targets common to all cell-types analysed. Further- more, we find that c-Myb footprints co-localise with active histone mark H3K4me3 and are significantly enriched at exons. We analysed co-localisation of c-Myb footprints with 104 chromatin regulatory factors in K562 cells, and identified nine proteins that are enriched together with c-Myb footprints on genes positively regulated by c-Myb and one protein enriched on negatively regulated genes. Our data suggest that c-Myb is a transcription fac- tor with multifaceted target regulation depending on cell type.

• Mora Ortiz, Antonio Carlos; Sandve, Geir Kjetil; Gabrielsen, Odd Stokke & Eskeland, Ragnhild (2015). In the loop: promoter-enhancer interactions and bioinformatics. Briefings in Bioinformatics.  ISSN 1467-5463. . doi: 10.1093/bib/bbv097 Show summary

  Enhancer–promoter regulation is a fundamental mechanism underlying differential transcriptional regulation. Spatial chromatin organization brings remote enhancers in contact with target promoters in cis to regulate gene expression. There is considerable evidence for promoter–enhancer interactions (PEIs). In the recent years, genome-wide analyses have identified signatures and mapped novel enhancers; however, being able to precisely identify their target gene(s) requires massive biological and bioinformatics efforts. In this review, we give a short overview of the chromatin landscape and transcriptional regulation. We discuss some key concepts and problems related to chromatin interaction detection technologies, and emerging knowledge from genome-wide chromatin interaction data sets. Then, we critically review different types of bioinformatics analysis methods and tools related to representation and visualization of PEI data, raw data processing and PEI prediction. Lastly, we provide specific examples of how PEIs have been used to elucidate a functional role of non-coding single-nucleotide polymorphisms. The topic is at the forefront of epigenetic research, and by highlighting some future bioinformatics challenges in the field, this review provides a comprehensive background for future PEI studies.

• Collas, Philippe & Eskeland, Ragnhild (2013). Oslo Epigenetics Symposium 2012 Oslo, Norway, 8-9 November 2012. Epigenomics.  ISSN 1750-1911.  5(1), s 29- 32 . doi: 10.2217/EPI.12.76
• Lund, Eivind Gard; Oldenburg Ruppelt, Anja; Delbarre, Erwan; Freberg, Christel Taranger; Duband-Goulet, Isabelle; Eskeland, Ragnhild; Buendia, Brigitte & Collas, Philippe (2013). Lamin A/C-promoter interactions specify chromatin state-dependent transcription outcomes. Genome Research.  ISSN 1088-9051.  23(10), s 1580- 1589 . doi: 10.1101/gr.159400.113
• Chioda, Christina; Spada, Fabio; Eskeland, Ragnhild & Thompson, Eric (2004). Histone mRNAs do not accumulate during S phase of either mitotic or endoreduplicative cycles in the chordate Oikopleura dioica. Molecular and Cellular Biology.  ISSN 0270-7306.  24(12), s 5391- 5403 Show summary

  Metazoan histones are generally classified as replication-dependent or replacement variants. Replication-dependent histone genes contain cell cycle-responsive promoter elements, their transcripts terminate in an unpolyadenylated conserved stem-loop, and their mRNAs accumulate sharply during S phase. Replacement variant genes lack cell cycle-responsive promoter elements, their polyadenylated transcripts lack the stem-loop, and they are expressed at low levels throughout the cell cycle. During early development of some organisms with rapid cleavage cycles, replication-dependent mRNAs are not fully S phase restricted until complete cell cycle regulation is achieved. The accumulation of polyadenylated transcripts during this period has been considered incompatible with metazoan development. We show here that histone metabolism in the urochordate Oikopleura dioica does not accord with some key tenets of the replication-dependent/replacement variant paradigm. During the premetamorphic mitotic phase of development, expressed variants shared characteristics of replication-dependent histones, including the 3' stem-loop, but, in contrast, were extensively polyadenylated. After metamorphosis, when cells in many tissues enter endocycles, there was a global downregulation of histone transcript levels, with most variant transcripts processed at the stem-loop. Contrary to the 30-fold S-phase upregulation of histone transcripts described in common metazoan model organisms, we observed essentially constant histone transcript levels throughout both mitotic and endoreduplicative cell cycles.

• Chioda, Christina; Eskeland, Ragnhild & Thompson, Eric (2002). Histone gene complement, variant expression, and mRNA processing in a urochordate Oikopleura dioica that undergoes extensive polyploidization. Molecular Biology and Evolution (MBE).  ISSN 0737-4038.  19, s 2247- 2260 Show summary

  Considerable data exist on coding sequences of histones in a wide variety of organisms. Much more restricted information is available on total histone gene complement, gene organization, transcriptional regulation, and histone mRNA processing. In particular, there is a significant phylogenetic gap in information for the urochordates, a subphylum near the invertebrate-vertebrate transition. In this study, we show that the appendicularian Oikopleura dioica has a histone gene complement that is similar to that of humans, though its genome size is 40- to 50-fold smaller. At a total length of 3.5 kb, the H3, H4, H1, H2A, and H2B quintet cluster is the most compact described thus far, but despite very rapid early developmental cleavage cycles, no extensive tandem repeats of the cluster were present. The high degree of variation within each of the complements of O. dioica H2A and H2B subtypes resembled that found in plants as opposed to more closely related vertebrate and invertebrate species, and developmental stage-specific expression of different subtypes was observed. The linker histone H1 was present in relatively few copies per haploid genome and contained short N- and C-terminal tails, a feature similar to that of copepods but different from many standard model organisms. The 3'UTRs of the histone genes contained both the consensus stem-loop sequence and the polyadenylation signals but lacked the consensus histone downstream element that is involved in the processing of histone mRNAs in echinoderms and vertebrates. Two types of transcripts were found, i.e., those containing both the stem-loop and a polyA tail as well as those cleaved at the normal site just 3' of the stem-loop. The O. dioica data are an important addition to the limited number of eukaryotes for which sufficiently extensive information on histone gene complements is available. Increasingly, it appears that understanding the evolution of histone gene organization, transcriptional regulation, and mRNA processing will depend at least as much on comparative analysis of constraints imposed by certain life history features and cell biological characteristics as on projections based on simple phylogenetic relationships.

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• Slettebakk, Marianne; Håpenes, Arnodd; Hessen, Dag Olav; Eskeland, Ragnhild; Gjærevoll, Inger & Borge, Ole Johan (2019). BIOS 2. Cappelen Damm AS.  ISBN 9788202604851.

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• Haraldsen, Kirsten Borse; Rogne, Sissel; Eskeland, Ragnhild; Kjeldstad, Torunn; Olsbye, Unni & Røyne, Anja (2017). Panelsamtale: Hva nå? DAMER! 100 år med kvinner i realfagene ved UiO. Show summary

  Innledning/forberedelser til panelsamtale ledet av Sissel Rogne under åpningen av utstillingen "Damer!"

• Eskeland, Ragnhild & Grini, Paul Eivind (2015). Epigenetikk – hadde Lamarck rett?, I: Dag Olav Hessen; Thore Lie & Nils Christian Stenseth (red.),  Mendels arv - Genetikkens æra.  Gyldendal Norsk Forlag A/S.  ISBN 978-82-05-45818-5.  8.  s 182 - 215

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