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Comprehensive mappi...
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
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- Tobiasson, Magnus (author)
- Karolinska Institutet,Karolinska Univ Hosp Huddinge, Ctr Hematol & Regenerat Med, Dept Med Huddinge, Div Hematol,Karolinska Inst, Huddinge, Sweden.
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- Abdulkadir, Hani (author)
- Karolinska Institutet,Karolinska Univ Hosp Huddinge, Ctr Hematol & Regenerat Med, Dept Med Huddinge, Div Hematol,Karolinska Inst, Huddinge, Sweden.
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- Lennartsson, Andreas (author)
- Karolinska Institutet,Karolinska Inst, Dept Biosci & Nutr, Stockholm, Stockholm Count, Sweden.
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- Katayama, Shintaro (author)
- Karolinska Institutet,Karolinska Inst, Dept Biosci & Nutr, Stockholm, Stockholm Count, Sweden.
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- Marabita, Francesco (author)
- Karolinska Institutet,Karolinska Inst, Dept Med, Ctr Mol Med, Unit Computat Med, Stockholm, Sweden.;Natl Bioinformat Infrastruct Sweden, Stockholm, Sweden.
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- De Paepe, Ayla (author)
- Karolinska Institutet,Karolinska Univ Hosp Huddinge, Ctr Hematol & Regenerat Med, Dept Med Huddinge, Div Hematol,Karolinska Inst, Huddinge, Sweden.
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- Karimi, Mohsen (author)
- Karolinska Institutet,Karolinska Univ Hosp Huddinge, Ctr Hematol & Regenerat Med, Dept Med Huddinge, Div Hematol,Karolinska Inst, Huddinge, Sweden.
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- Krjutskov, Kaarel (author)
- Karolinska 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.
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- Einarsdottir, Elisabet (author)
- Karolinska Institutet,Karolinska Inst, Dept Biosci & Nutr, Stockholm, Stockholm Count, Sweden.;Univ Helsinki, Mol Neurol Res Program, Helsinki, Finland.;Folkhalsan Inst Genet, Helsinki, Finland.
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- Grövdal, Michael (author)
- Karolinska Univ Hosp Huddinge, Ctr Hematol & Regenerat Med, Dept Med Huddinge, Div Hematol,Karolinska Inst, Huddinge, Sweden.
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- Jansson, Monika (author)
- Karolinska Institutet,Karolinska Univ Hosp Huddinge, Ctr Hematol & Regenerat Med, Dept Med Huddinge, Div Hematol,Karolinska Inst, Huddinge, Sweden.
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- Ben Azenkoud, Asmaa (author)
- Karolinska Univ Hosp Huddinge, Ctr Hematol & Regenerat Med, Dept Med Huddinge, Div Hematol,Karolinska Inst, Huddinge, Sweden.
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- Corddedu, Lina (author)
- Karolinska Inst, Dept Biosci & Nutr, Stockholm, Stockholm Count, Sweden.
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- Lehmann, Sören (author)
- Karolinska Institutet,Uppsala universitet,Hematologi,Karolinska Univ Hosp Huddinge, Ctr Hematol & Regenerat Med, Dept Med Huddinge, Div Hematol,Karolinska Inst, Huddinge, Sweden
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- Ekwall, Karl (author)
- Karolinska Inst, Dept Biosci & Nutr, Stockholm, Stockholm Count, Sweden.
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- Kere, Juha (author)
- Karolinska Institutet,Karolinska Inst, Dept Biosci & Nutr, Stockholm, Stockholm Count, Sweden.;Univ Helsinki, Mol Neurol Res Program, Helsinki, Finland.;Folkhalsan Inst Genet, Helsinki, Finland.
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- Hellström-Lindberg, Eva (author)
- Karolinska Univ Hosp Huddinge, Ctr Hematol & Regenerat Med, Dept Med Huddinge, Div Hematol,Karolinska Inst, Huddinge, Sweden.
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- Ungerstedt, Johanna (author)
- Karolinska Institutet,Karolinska Univ Hosp Huddinge, Ctr Hematol & Regenerat Med, Dept Med Huddinge, Div Hematol,Karolinska Inst, Huddinge, Sweden.
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Karolinska Institutet Karolinska Univ Hosp Huddinge, Ctr Hematol & Regenerat Med, Dept Med Huddinge, Div Hematol,Karolinska Inst, Huddinge, Sweden (creator_code:org_t)
- 2017-02-28
- 2017
- English.
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In: Oncotarget. - : IMPACT JOURNALS LLC. - 1949-2553. ; 8:17, s. 28812-28825
- Related links:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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Abstract
Subject headings
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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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- MDS
- azacitidine
- epigenetics
- DNA methylation
- histone modifications
Publication and Content Type
- ref (subject category)
- art (subject category)
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Tobiasson, Magnu ...
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Abdulkadir, Hani
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Lennartsson, And ...
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Katayama, Shinta ...
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Marabita, France ...
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De Paepe, Ayla
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Karimi, Mohsen
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Krjutskov, Kaare ...
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Einarsdottir, El ...
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Grövdal, Michael
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Jansson, Monika
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Ben Azenkoud, As ...
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Corddedu, Lina
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Lehmann, Sören
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Ekwall, Karl
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Kere, Juha
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Hellström-Lindbe ...
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Ungerstedt, Joha ...
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- MEDICAL AND HEALTH SCIENCES
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Oncotarget
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Uppsala University
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Karolinska Institutet