Estrogen receptors (ERs) associate with distinct transcriptional coactivato
rs to mediate activation of target genes in response to estrogens. Previous
work has provided multiple evidence for a critical role of p160 coactivato
rs and associated histone acetyltransferases in estrogen signaling. In cont
rast, the involvement of the mammalian mediator complex remains to be estab
lished. Further, although the two subtypes ER alpha and ER beta appear to b
e similar in regard to principles of LXXLL-mediated coactivator binding to
the AF-2 activation domain, there are indications that the context-dependen
t transcriptional activation profiles of the two ERs can be quite distinct.
Potentially, this could be attributed to differences with regard to coregu
lator recruitment. We have here studied the interactions of the nuclear rec
eptor-binding subunit of the mammalian mediator complex, referred to as TRA
P220, with ER alpha and ER beta. In comparison to the p160 coactivator TIF2
, we find that TRAP220 displays ERP preference. Here, we show that this is
a feature of the binding specificity of the TRAP220 LXXLL motifs and demons
trate that the ER subtype-specific F-domain influences TRAP220 interaction.
Such differences with regard to coactivator recruitment indicate that the
relative importance of individual coregulators in estrogen signaling could
depend on the dominant ER subtype.