CTCF boundary remodels chromatin domain and drives aberrant HOX gene transcription in acute myeloid leukemia

We analyzed RNA-seq, ATAC-seq, ChIP-seq and 4C-seq data to find that CTCF binding site located between HOXA7 and HOXA9 genes (CBS7/9) is critical for establishing and maintaining aberrant HOXA9-HOXA13 gene expression in AML. Disruption of the CBS7/9 boundary resulted in spreading of repressive H3K27me3 into the posterior active HOXA chromatin domain that subsequently impaired enhancer/promoter chromatin accessibility and disrupted ectopic long-range interactions among the posterior HOXA genes. Consistent with the role of the CBS7/9 boundary in HOXA locus chromatin organization, attenuation of the CBS7/9 boundary function reduced posterior HOTTIP lincRNA and HOXA gene expression and altered myeloid specific transcriptome profiles important for pathogenesis of myeloid malignancies. We have submitted our RAW sequence datasets into SRA database (SRP115103 and Bioproject: PRJNA396046), including RNA-SEQ, ATAC-seq, ChIP-seq and 4C-seq for WT and CBS7/9KO MOLM13 leukemia cells