Transcriptomics

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Expression data from bone marrow derived granulocyte monocyte precursors (GMPs) from wt -, Gfi1 knock-out -, human-Gfi1-SNP36N knock in and human wt-Gfi1 knock in mice


ABSTRACT: The incidence of cancer is not only influenced by exposure to environmental factors such as toxic substances and chemotherapy, but is also a result of individual predispositions. Single Nucleotide Polymorphisms (SNPs) represent one such individual predisposition to cancer1. Gfi136N is a SNP in the coding region of the gene “Growth factor independence 1 (Gfi1)” predisposing to development of Acute myeloid leukemia (AML). However, the mechanisms how this polymorphism is associated with AML are unknown. Here we present a mouse model in which the presence of Gfi136N leads to altered epigenetic modifications in the myeloid progenitor fraction “Granulocytic Monocytic Progenitor (GMP)” and demonstrates how this might predispose to AML. Presence of Gfi136N leads to a different epigenetic programming of the GMPs resulting in higher levels of the leukemogenic transcription factor Hoxa9. To our knowledge, this is the first mouse model of a SNP leading to epigenetic changes. Thus, SNPs not only result in an altered structure or expression level of certain proteins but here we show that SNPs might also lead to different cancer related epigenetic modifications. We used microarrays to detail the changes in the program of gene expression of GMPs induced by the knock in of human Gfi1 variants in the mouse Gfi1 locus Bone marrow derived granulocyte monocyte precursors (GMPs) from wt.-,Gfi1 knock-out.-, human Gfi1-knock in and human Gfi1-SNP36N knock in mice were collected by fluorescence activated cell sorting (FACS) for total RNA extraction and gene expression analysis on affymetrix mouse Gene 1.0 ST arrays. We aimed to identify differentially regulated target genes of the human Gfi1-SNP36N variant in a mouse model system which mit contribute to the development of acute myeloid leukemia (AML).

ORGANISM(S): Mus musculus  

SUBMITTER: Lothar Vassen   Justine K Peeters  Joop Jansen  Ulrich Dührsen  Riyan Chen  Joseph Krongold  Bert van der Reijden  Cyrus Khandanpour  Tarik Moroy  Bob Lowenberg  Chandrashekhar V Patel  Marie-Claude Gaudreau 

PROVIDER: E-GEOD-25551 | ArrayExpress | 2012-11-22

SECONDARY ACCESSION(S): GSE25551PRJNA134033

REPOSITORIES: GEO, ArrayExpress

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