The role of retinoblastoma-associated proteins 46 and 48 in estrogen receptor α mediated gene expression

The differential recruitment of coregulatory proteins to the DNA-bound estrogen receptor α (ERα) plays a critical role in mediating estrogen-responsive gene expression. We previously isolated and identified retinoblastoma-associated proteins 46 (RbAp46) and 48 (RbAp48), which are associated with chromatin remodeling, histone deacetylation, and transcription repression, as proteins associated with the DNA-bound ERα. We now demonstrate that RbAp46 and RbAp48 interact with ERα in vitro and in vivo, associate with ERα at endogenous, estrogen-responsive genes, and alter expression of endogenous, ERα-activated and -repressed genes in MCF-7 breast cancer cells. Our findings reveal that RbAp48 limits expression of estrogen-responsive genes and that RbAp46 modulates estrogen responsiveness in a gene-specific manner. The ability of RbAp46 and RbAp48 to interact with ERα and influence its activity reveals yet another role for these multifunctional proteins in regulating gene expression.