Distinção, cultura de consumo e gentrificação: o Centro Cultural Banco do Brasil e o mercado de bens simbólicos

Abstract

Histone methyltransferase G9a has been understood primarily as a corepressor of gene expression, but we showed previously that G9a positively regulates nuclear receptor-mediated transcription in reporter gene assays. Here, we show that endogenous G9a contributes to the estradiol (E(2))-dependent induction of some endogenous target genes of estrogen receptor (ER)$α$ in MCF-7 breast cancer cells while simultaneously limiting the E(2)-induced expression of other ER$α$ target genes. Thus, G9a has a dual and selective role as a coregulator for ER$α$ target genes. The ER$α$ binding regions associated with the pS2 gene, which requires G9a for E(2)-induced expression, are transiently occupied by G9a at 15 min after beginning E(2) treatment, suggesting that G9a coactivator function is by direct interaction with ER$α$ target genes. Transient reporter gene assays with deletion mutants of G9a demonstrated that domains previously associated with the corepressor functions of G9a (C-terminal methyltransferase domain, ankyrin repeat domain, and cysteine-rich domain) were unnecessary for G9a coactivator function in ER$α$-mediated transcription. In contrast, the N-terminal domain of G9a was necessary and sufficient for enhancement of ER$α$-mediated transcription and for E(2)-induced occupancy of G9a on ER$α$ binding sites associated with endogenous target genes of ER$α$. In addition to a previously identified activation domain, this region contains a previously uncharacterized ligand-dependent ER$α$ binding function, indicating how G9a is recruited to the target genes. Therefore, the coactivator and corepressor functions of G9a involve different G9a domains and different molecular mechanisms.