BioProject

This study characterizes the genome-side occupancy of AML1, AML1-ETO and the cofactors N-CoR and p300 in leukemics cells (Kasumi-1) to discover novel regulatory mechanisms involving genes bound by the t(8:21) fusion protein AML1-ETO. More...

This study characterizes the genome-side occupancy of AML1, AML1-ETO and the cofactors N-CoR and p300 in leukemics cells (Kasumi-1) to discover novel regulatory mechanisms involving genes bound by the t(8:21) fusion protein AML1-ETO. A significant discovery of our study is the co-localization of AML1-ETO with the N-CoR co-repressor on genomic regions that are primarily distal to the transcriptional start sites (TSSs). These regions exhibit over-representation of the PU.1 motif: PU.1 is a key hematopoietic regulator and member of the ETS family of transcription factors. Functionally, genes co-occupied by AML1-ETO and N-CoR (e.g., TYROBP and LAPTM5) are associated with the leukemic phenotype, as determined by analyses of gene ontology and by the observation that these genes are predominantly up-regulated upon AML1-ETO depletion. To further probe the regulatory context of these leukemic cells, genome-wide enrichment of the transcriptional initiation-associated histone modification H3K4me3 was also measured. Overall design: Genome-wide study of transcription factor-DNA binding for AML1 (RUNX1) and the t(8;21) fusion protien AML1-ETO (RUNX1T1) in the Kasumi-1 leukemia cell line. The genome-wide binding of the disease-related cofactors N-CoR and p300 was assayed, along with enrichments of the H3K4me3 and H3K27me3 histone modifications. Less...