Aberrant chromatin acetylation in MLL-AF9 leukemia mediates the response to HDAC inhibition (ChIP-Seq). Homo sapiens

We studied the chromatin modification patterns induced by the presence of the MLL-AF9 fusion protein in a model of human hematopoietic stem/progenitor cells (HSPC) transduced with retrovirus expressing MLL-AF9cDNA (HSPC-MA9). Comparative ChIP-seq analysis between HSPC-MA9 and control HSPC, revealed a massive hyperacetylation of histones that was consistent with the transcriptional profile in the presence of MLL-AF9 fusion protein. Furthermore, we identified 66 MLL-AF9 targets, and found that H4ac was present along with H3K4me3 and H3K79me2 chromatin marks in over 50% of the MLL-AF9 target genes. Overall design: Examination of histone aceylation and methylation changes upon expression of MLL-AF9 fusion protein in human hematopoietic stem/progenitor cells.