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Signatures of polycomb repression and reduced H3K4 trimethylation are associated with p15INK4b DNA methylation in AML.


ABSTRACT: DNA hypermethylation of the p15INK4b tumor suppressor gene is commonly observed in acute myeloid leukemia (AML). Repressive histone modifications and their associated binding proteins have been implicated in the regulation of DNA methylation and the transcriptional repression of genes with DNA methylation. We have used high-density chromatin immunoprecipitation-on-chip to determine the histone modifications that normally regulate p15INK4b expression in AML cells and how these marks are altered in cells that have p15INK4b DNA methylation. In AML patient blasts without p15INK4b DNA methylation, a bivalent pattern of active (H3K4me3) and repressive (H3K27me3) modifications exist at the p15INK4b promoter. AML patient blasts with p15INK4b DNA methylation lose H3K4me3 at p15INK4b and become excl

SUBMITTER: Paul TA 

PROVIDER: S-EPMC2858468 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature