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Our studies focus on regulation of the proliferative functions of Estrogen receptor α (ERα) as a cure for breast cancer,at both the receptor level and co-factor level.ER dimerization is prerequisite for its activation of target gene transcription.Since the two forms of ER, ERα and ERβ, exhibit opposing functions in cell proliferation, the ability of ligands to induce ERα/β heterodimers versus their respective homodimers is expected to have profound impacts on transcriptional outcomes and cellular growth.We recently developed Bioluminescence Resonance Energy Transfer (BRET) assays to monitor the formation of ERα/β heterodimers in vivo and to distinguish the ability of estrogenic ligands to promote ER homo-versus hetero-dimerization.Using BRET system, we demonstrated that although both partners contribute to heterodimerization, ligand-bound ERα plays a dominant role.ER BRET assays have been applied in drug screening for dimer-selective ER modulators.ERα is believed to regulate growth and differentiation through balanced interaction with transcriptional cofactors.Although Coactivator associated arginine methyltransferase 1 (CARM1) had been shown to regulate ERα transcription in cell-based assays, biological function of CARM1 in estrogen dependent processes remain to be determined.Our recent studies have shown that CARM1 counteracts the proliferative roles of ERα in breast cancer cells through epigenetic re-programming estrogen dependent cellular processes.