The AR is unusual among steroid hormone receptors in that the major transactivation function is activation function-1 (AF1) situated within the N-terminal domain rather than AF2 in the ligand-binding domain (LBD), which is relatively weak in the AR (6,31,33). Furthermore, AF1 can be subdivided into two discrete, overlapping activation domains, the usage of which is context-dependent. Although almost the entire N terminus (residues 1-494) is required for full activity of the full-length receptor, a core that contributes 50% of the activity is located between residues 101 and 360, and this region has been termed TAU1. However, in the absence of the LBD, a different region mediates activation, and this region is termed TAU5 (residues 370 -494) (31) (Fig. 2A). We performed pulldown interaction assays to determine the interaction of full-length HEYL with full-length and deletion constructs of AR. These showed that GST-HEYL was able to interact strongly with full-length AR expressed in COS-1 cells (Fig. 2B). Furthermore, a robust interaction was also observed between full-length HEYL and GST-NTD, which contains the AR N-terminal domain (residues 1-556) but lacks the LBD and most of the DNA-binding domain (DBD), indicating that HEYL likely interacts with AR via the N-terminal transactivation domain (Fig. 2B). In support of this, no interaction was seen between HEYL and GST fused to the LBD in the presence or absence of ligand. To determine whether HEYL also represses AR-AF1 activity, we transfected COS-1 cells with an AR deletion construct lacking amino acids 654 -919 (AR⌬LBD), which is constitutively active. HEYL could significantly repress the activity of AR⌬LBD on TAT-GRE-E1B-LUC (Fig. 2C) and Probasin-LUC promoter constructs (data not shown). Together, these **data** indicate that HEYL interacts with and represses AR activity largely through AF1. To narrow down the functional domain affected, we next assayed the ability of HEYL to repress AR deletion constructs lacking either TAU1 (AR⌬1) or TAU5 (AR⌬5) (Fig. 2D and supplemental Fig. S3). This showed that deletion of either domain resulted in reduced relative repression of AR activity by HEYL; however, the repression of AR⌬1 (with intact TAU5) by HEYL was proportionately less than that of AR⌬5 (with intact TAU1), indicating that TAU1 (residues 101-360) is likely to be the functional domain that is primarily affected by HEYL in the context of the full-length AR.