ADA3-containing complexes associate with estrogen receptor alpha.

Transcriptional repression and activation by nuclear receptors (NRs) are brought about by coregulator complexes. These complexes modify the chromatin environment of target genes and affect the activity of the basal transcription machinery. We have previously implicated the yeast ADA3 protein in transcriptional activation by estrogen and retinoid X receptors in yeast and mammalian cells. Here we report the cloning of the mouse homolog of ADA3 and its characterization with respect to the estrogen receptor alpha (ERalpha) function. Mouse mADA3 is 23% identical and 47% similar to yeast yADA3, and mADA3 in contrast to yADA3 does not interact with NRs directly even though it contains two LxxLL NR boxes. However, the ADA3-containing TBP-free-TAF-containing complex (TFTC) can interact with ERalpha in a ligand-independent manner, indicating that other subunits of the complex are sufficient to mediate interaction with NRs.