GSE113191
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. Overall design: 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