SUPT6H controls estrogen receptor activity and cellular differentiation by multiple epigenomic mechanisms.

摘要: The estrogen receptor alpha (ERα) is the central transcriptional regulator of ductal mammary epithelial lineage specification and an important prognostic marker in human breast cancer. Although antiestrogen therapies are initially highly effective at treating ERα-positive tumors, a large number tumors progress to refractory, more poorly differentiated phenotype accompanied by reduced survival. A better understanding molecular mechanisms involved progression from estrogen-dependent hormone-resistant cancer may uncover new targets for treatment discovery predictive markers. Recent studies have uncovered role elongation chromatin modifications controlling ERα activity responsiveness. Suppressor Ty Homologue-6 (SUPT6H) histone chaperone that links changes structure. We show SUPT6H required estrogen-regulated transcription maintenance structure cells, possibly part through interaction with RNF40 regulation H2B monoubiquitination (H2Bub1). Moreover, we demonstrate protein levels decrease malignancy Consistently, SUPT6H, similar H2Bub1, cellular differentiation suppression repressive mark H3K27me3 on lineage-specific genes. Together, these data identify as epigenetic differentiation.