Search: id:"swepub:oai:DiVA.org:uu-322725" >
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Tobiasson, MagnusKarolinska Institutet,Karolinska Univ Hosp Huddinge, Ctr Hematol & Regenerat Med, Dept Med Huddinge, Div Hematol,Karolinska Inst, Huddinge, Sweden.
(author)
Comprehensive mapping of the effects of azacitidine on DNA methylation, repressive/permissive histone marks and gene expression in primary cells from patients with MDS and MDS-related disease
- Article/chapterEnglish2017
Publisher, publication year, extent ...
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2017-02-28
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IMPACT JOURNALS LLC,2017
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electronicrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-322725
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-322725URI
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https://doi.org/10.18632/oncotarget.15807DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:135735652URI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Azacitidine (Aza) is first-line treatment for patients with high-risk myelodysplastic syndromes (MDS), although its precise mechanism of action is unknown. We performed the first study to globally evaluate the epigenetic effects of Aza on MDS bone marrow progenitor cells assessing gene expression (RNA seq), DNA methylation (Illumina 450k) and the histone modifications H3K18ac and H3K9me3 (ChIP seq). Aza induced a general increase in gene expression with 924 significantly upregulated genes but this increase showed no correlation with changes in DNA methylation or H3K18ac, and only a weak association with changes in H3K9me3. Interestingly, we observed activation of transcripts containing 15 endogenous retroviruses (ERVs) confirming previous cell line studies. DNA methylation decreased moderately in 99% of all genes, with a median beta-value reduction of 0.018; the most pronounced effects seen in heterochromatin. Aza-induced hypomethylation correlated significantly with change in H3K9me3. The pattern of H3K18ac and H3K9me3 displayed large differences between patients and healthy controls without any consistent pattern induced by Aza. We conclude that the marked induction of gene expression only partly could be explained by epigenetic changes, and propose that activation of ERVs may contribute to the clinical effects of Aza in MDS.
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Added entries (persons, corporate bodies, meetings, titles ...)
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Abdulkadir, HaniKarolinska Institutet,Karolinska Univ Hosp Huddinge, Ctr Hematol & Regenerat Med, Dept Med Huddinge, Div Hematol,Karolinska Inst, Huddinge, Sweden.
(author)
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Lennartsson, AndreasKarolinska Institutet,Karolinska Inst, Dept Biosci & Nutr, Stockholm, Stockholm Count, Sweden.
(author)
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Katayama, ShintaroKarolinska Institutet,Karolinska Inst, Dept Biosci & Nutr, Stockholm, Stockholm Count, Sweden.
(author)
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Marabita, FrancescoKarolinska Institutet,Karolinska Inst, Dept Med, Ctr Mol Med, Unit Computat Med, Stockholm, Sweden.;Natl Bioinformat Infrastruct Sweden, Stockholm, Sweden.
(author)
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De Paepe, AylaKarolinska Institutet,Karolinska Univ Hosp Huddinge, Ctr Hematol & Regenerat Med, Dept Med Huddinge, Div Hematol,Karolinska Inst, Huddinge, Sweden.
(author)
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Karimi, MohsenKarolinska Institutet,Karolinska Univ Hosp Huddinge, Ctr Hematol & Regenerat Med, Dept Med Huddinge, Div Hematol,Karolinska Inst, Huddinge, Sweden.
(author)
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Krjutskov, KaarelKarolinska Institutet,Karolinska Inst, Dept Biosci & Nutr, Stockholm, Stockholm Count, Sweden.;Univ Helsinki, Mol Neurol Res Program, Helsinki, Finland.;Folkhalsan Inst Genet, Helsinki, Finland.;Competence Ctr Hlth Technol, Tartu, Estonia.
(author)
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Einarsdottir, ElisabetKarolinska Institutet,Karolinska Inst, Dept Biosci & Nutr, Stockholm, Stockholm Count, Sweden.;Univ Helsinki, Mol Neurol Res Program, Helsinki, Finland.;Folkhalsan Inst Genet, Helsinki, Finland.
(author)
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Grövdal, MichaelKarolinska Univ Hosp Huddinge, Ctr Hematol & Regenerat Med, Dept Med Huddinge, Div Hematol,Karolinska Inst, Huddinge, Sweden.
(author)
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Jansson, MonikaKarolinska Institutet,Karolinska Univ Hosp Huddinge, Ctr Hematol & Regenerat Med, Dept Med Huddinge, Div Hematol,Karolinska Inst, Huddinge, Sweden.
(author)
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Ben Azenkoud, AsmaaKarolinska Univ Hosp Huddinge, Ctr Hematol & Regenerat Med, Dept Med Huddinge, Div Hematol,Karolinska Inst, Huddinge, Sweden.
(author)
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Corddedu, LinaKarolinska Inst, Dept Biosci & Nutr, Stockholm, Stockholm Count, Sweden.
(author)
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Lehmann, SörenKarolinska Institutet,Uppsala universitet,Hematologi,Karolinska Univ Hosp Huddinge, Ctr Hematol & Regenerat Med, Dept Med Huddinge, Div Hematol,Karolinska Inst, Huddinge, Sweden(Swepub:uu)sorle534
(author)
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Ekwall, KarlKarolinska Inst, Dept Biosci & Nutr, Stockholm, Stockholm Count, Sweden.
(author)
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Kere, JuhaKarolinska Institutet,Karolinska Inst, Dept Biosci & Nutr, Stockholm, Stockholm Count, Sweden.;Univ Helsinki, Mol Neurol Res Program, Helsinki, Finland.;Folkhalsan Inst Genet, Helsinki, Finland.
(author)
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Hellström-Lindberg, EvaKarolinska Univ Hosp Huddinge, Ctr Hematol & Regenerat Med, Dept Med Huddinge, Div Hematol,Karolinska Inst, Huddinge, Sweden.
(author)
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Ungerstedt, JohannaKarolinska Institutet,Karolinska Univ Hosp Huddinge, Ctr Hematol & Regenerat Med, Dept Med Huddinge, Div Hematol,Karolinska Inst, Huddinge, Sweden.
(author)
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Karolinska InstitutetKarolinska Univ Hosp Huddinge, Ctr Hematol & Regenerat Med, Dept Med Huddinge, Div Hematol,Karolinska Inst, Huddinge, Sweden.
(creator_code:org_t)
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In:Oncotarget: IMPACT JOURNALS LLC8:17, s. 28812-288251949-2553
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