GSE96996
UTX ChIP sequencing in non-treated MCF-7 cells
UTX is implicated in embryonic development and lineage specification. However, how this X-linked histone demethylase contributes to the development and progression of breast cancer remains to be investigated. Here we report that UTX is physically associated with estrogen receptor (ER) and functions in ER-regulated transcription. We showed that UTX coordinates with JHDM1D and CBP to direct H3K27 methylation-acetylation transition and to create a permissive chromatin state on ER targets. Genome-wide analysis of the transcriptional targets of UTX by ChIP-seq identified a cohort of genes including chemokine receptor CXCR4 that are critically involved in breast cancer tumorigenesis and metastasis. We demonstrated that UTX promotes the proliferation and migration of ER+ breast cancer cells. Interestingly, UTX itself is transactivated by ER, forming a feed-forward loop in the regulation of hormone response. Indeed, UTX is upregulated during ER+ breast cancer progression, and the level of its expression is positively correlated with that of CXCR4 and negatively correlated with the overall survival of ER+ breast cancer patients. Our study identified a feed-forward loop between UTX and ER in the regulation of hormonally responsive breast cancer carcinogenesis, supporting the pursuit of UTX as a potential target for the intervention of certain ER+ breast cancer with specific epigenetic vulnerability. Overall design: Examination of UTX target genes in MCF-7 cells