Aberrant DNA hypermethylation signature in acute myeloid leukemia directed by EVI1
| Autor: | Sanne Lugthart, Lucy Skrabanek, Maria E. Figueroa, Stefan Meyer, Eric M.J. Bindels, Claudia A.J. Erpelinck-Verschueren, Yushan Li, Ari Melnick, Peter J. M. Valk, Ruud Delwel, Bob Löwenberg, John M. Greally |
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| Přispěvatelé: | Hematology, Internal Medicine |
| Rok vydání: | 2010 |
| Předmět: |
Adult
Male Chromatin Immunoprecipitation Adolescent Immunology Blotting Western Biology Biochemistry Polymerase Chain Reaction DNA Methyltransferase 3A chemistry.chemical_compound Young Adult SDG 3 - Good Health and Well-being hemic and lymphatic diseases Proto-Oncogenes medicine Humans DNA (Cytosine-5-)-Methyltransferases Promoter Regions Genetic Gene Aged Myeloid leukemia Promoter Cell Biology Hematology Methylation DNA Neoplasm DNA Methylation Middle Aged medicine.disease Molecular biology MDS1 and EVI1 Complex Locus Protein DNA-Binding Proteins Leukemia Leukemia Myeloid Acute chemistry DNA methylation Cancer research Female Chromatin immunoprecipitation DNA Transcription Factors |
| Zdroj: | Blood, 117(1), 234-241. American Society of Hematology |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | DNA methylation patterns are frequently dysregulated in cancer, although little is known of the mechanisms through which specific gene sets become aberrantly methylated. The ecotropic viral integration site 1 (EVI1) locus encodes a DNA binding zinc-finger transcription factor that is aberrantly expressed in a subset of acute myeloid leukemia (AML) patients with poor outcome. We find that the promoter DNA methylation signature of EVI1 AML blast cells differs from those of normal CD34+ bone marrow cells and other AMLs. This signature contained 294 differentially methylated genes, of which 238 (81%) were coordinately hypermethylated. An unbiased motif analysis revealed an overrepresentation of EVI1 binding sites among these aberrantly hypermethylated loci. EVI1 was capable of binding to these promoters in 2 different EVI1-expressing cell lines, whereas no binding was observed in an EVI1-negative cell line. Furthermore, EVI1 was observed to interact with DNA methyl transferases 3A and 3B. Among the EVI1 AML cases, 2 subgroups were recognized, of which 1 contained AMLs with many more methylated genes, which was associated with significantly higher levels of EVI1 than in the cases of the other subgroup. Our data point to a role for EVI1 in directing aberrant promoter DNA methylation patterning in EVI1 AMLs. |
| Databáze: | OpenAIRE |
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