Integrative genomic analysis in K562 chronic myelogenous leukemia cells reveals that proximal NCOR1 binding positively regulates genes that govern erythroid differentiation and Imatinib sensitivity

摘要: To define the functions of NCOR1 we developed an integrative analysis that combined ENCODE and NCI-60 data, followed by in vitro validation. H3K9me3 ChIP-Seq, FAIRE-seq DNA CpG methylation interactions were related to gene expression using bootstrapping approaches. Most combinations (24/44) associated with significantly elevated level protein coding genes only very few repression. DAVID's biological process annotation revealed was uniquely acetylation ETS binding. A matrix drug built on data identified Imatinib targeted governed transcriptome. Stable knockdown K562 cells slowed growth repressed cistrome, again, GO terms binding, dampened sensitivity Imatinib-induced erythroid differentiation. Mining public microarray NCOR1-targeted enriched response signatures cell lines chronic myelogenous leukemia (CML) patients. These approaches integrated transcriptome relationships reveal function is surprisingly most expression, these targets, both CML patients, associate Imatinib.