The Role of the C-terminal Extension (CTE) of the Estrogen Receptor α and β DNA Binding Domain in DNA Binding and Interaction with HMGB


HMGB-1/-2 are coregulatory proteins that facilitate the DNA binding and transcriptional activity of steroid receptor members of the nuclear receptor family of transcription factors. We investigated the influence and mechanism of action of HMGB-1/2 (formerly known as HMG-1/-2) on estrogen receptor α (ERα) and ERβ. Both ER subtypes were responsive to HMGB-1/-2 with respect to enhancement of receptor DNA binding affinity and transcriptional activity in cells. Responsiveness to HMGB-1/-2 was dependent on the C-terminal extension (CTE) region of the ER DNA binding domain (DBD) and correlated with a direct protein interaction between HMGB-I/-2 and the CTE. Thus the previously reported higher DNA binding affinity and transcription activity of ERa as compared with ERβ is not due to a lack of ERβ interaction with HMGB-1/2. Using chimeric receptor DBDs, the higher intrinsic DNA binding affinity of ERα than ERβ was shown to be due to a unique property of the ERα CTE, independent of HMGB-1/-2. The CTE of both ER subtypes was also shown to be required for interaction with ERE half-sites. These studies reveal the importance of the CTE and HMGB-1/-2 for ERα and ERβ interaction with their cognate target DNAs.

Publication Title

Journal of Biological Chemistry