ZNF366 is a novel corepressor for estrogen receptor alpha that mediates its effects through interaction with CtBP

Regulation of gene expression by the estrogen receptor (ER) requires the coordinated recruitment and dissociation of transcriptional coactivator complexes and concomitant chromatin remodelling and histone modification. In addition to the well-characterised recruitment of coactivator proteins, a number of corepressor proteins can also be recruited to the liganded ER, including RIP140 and L-CoR.

We have recently identified a new ER interacting protein, ZNF366, which is recruited to the liganded ER, through interactions involving the zinc finger domains of both proteins. We show that repression of ER-regulated genes by ZNF366 involves recruitment of the well-described corepressor CtBP. This interaction is mediated by two sequence motifs in ZNF366, conforming to the consensus CtBP-binding motif (PXDLS). Mutation of these motifs in ZNF366 reduces, but does not abolish, the corepressor activity of ZNF366. Additionally, ZNF366 interacts with RIP140, raising the possibility that RIP140 and ZNF366 may act synergistically in regulating ER activity [1].

Finally, we show that although ZNF366 is expressed in normal breast epithelial cells, its expression is not detected in breast cancer cells. This raises the possibility that regulation of ER activity by ZNF366 may be important in breast cancer development.