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Global methylation alterations in Dnmt3aKO derived malignancies

ABSTRACT: To test the long-term effects of lack of Dnmt3a on mouse HSCs, we established a cohort of lethally irradiated mice transplanted with Dnmt3a-KO or WT HSC control cells. Dnmt3a deletion in purified HSCs transplanted alone leads to an array of hematologic disorders that models the spectrum of disorders seen in human malignancies. We investigated DNA methylation alterations in disease and control mice by RRBS. We generated an average of 23.81 million reads per sample (18.97 - 31.67 million) of which an average of 18.07 million could be mapped to the mm9 genome (2.78 - 26.42 million). We achieved an average CpG coverage depth of 31.79-fold (8.09 - 47.44-fold) and average bisulfite conversion efficiency of 99.91% (99.87 - 99.95%). Reduced representation bisulfite sequencing of cells using Illumina HiSeq 2000 and 2500

ORGANISM(S): Mus musculus

SUBMITTER: Margaret Goodell

PROVIDER: E-GEOD-60264 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Dnmt3a loss predisposes murine hematopoietic stem cells to malignant transformation.

Mayle Allison A Yang Liubin L Rodriguez Benjamin B Zhou Ting T Chang Edmund E Curry Choladda V CV Challen Grant A GA Li Wei W Wheeler David D Rebel Vivienne I VI Goodell Margaret A MA

Blood 20150101 4

DNA methyltransferase 3A (DNMT3A) is mutated in hematologic malignancies affecting myeloid, mixed, and lymphoid lineages, and these mutations are associated with poor prognosis. Past studies in mice revealed Dnmt3a-knockout (KO)hematopoietic stem cells (HSCs) had increased self-renewal, but no leukemia was observed. Here, all lethally irradiated mice transplanted with Dnmt3a-deleted HSCs died within 1 year. Animals were diagnosed with a spectrum of malignancies similar to those seen in patients ...[more]

PMID: 25416277

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