HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Stokes, K. Articles by Teng, C. Search for Related Content PubMed PubMed Citation Articles by Stokes, K. Articles by Teng, C.

¹ Gene Regulation Section, Laboratory of Reproduction and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
² Animal Science Department, College of Agriculture and Life Sciences, North Carolina State University, Raleigh, North Carolina 27695, USA

(Requests for offprints should be addressed to C Teng, NIEHS/NIH PO Box 12233, MD E-201, Research Triangle Park, North Carolina 27709, USA; Email: Teng{at}niehs.nih.gov)

A critical step in estrogen action is the recognition of estrogen responsive elements (EREs) by liganded estrogen receptor. Our current studies were designed to determine whether an extended estrogen response element half-site (ERRE) contributes to the differential estrogen responses of the human and mouse lactoferrin overlapping chicken ovalbumin upstream promoter/ERE sequences (estrogen response modules, ERMs) in the context of their natural promoters. Transient transfections of MCF-7 cells show that liganded estrogen receptor (ER) activates transcription of the human lactoferrin ERM fourfold higher than the mouse lactoferrin ERM in the context of their natural promoters. Since the ERRE of the human lactoferrin gene naturally occurs 18 bp upstream from the ERM and is absent in the mouse lactoferrin gene promoter, we created a chimeric mouse lactoferrin CAT reporter, which now encodes the ERRE in the identical location as in the human lactoferrin gene. The addition of the ERRE in the mouse lactoferrin gene rendered this reporter extremely responsive to estrogen stimulation. Using limited protease digestions and electrophoretic mobility shift assays, we showed that the binding and protease sensitivity of ER bound to the mouse ERM with or without the ERRE, differed. Importantly, occupancy of additional nuclear receptors at the ERRE may contribute to ER binding and activation. Furthermore, the presence of ERRE influences the selectivity of coactivators in liganded ER-mediated transcriptional activity. When the receptor is bound to human and mouse plus genes, which contain the ERRE, steroid receptor coactivator (SRC)-2 was preferred, while SRC-1 and SRC-3 coactivators selectively enhanced the mouse lactoferrin gene activity. Moreover, peroxisome proliferator activated receptor- coactivator-1 (PGC-1) and PGC-1-related estrogen receptor coactivator (PERC) robustly increase the transcriptional function of ER in the presence of the ERRE. In conclusion, these data show that the context of the lactoferrin gene influences the ER-mediated transcriptional activity.

This article has been cited by other articles:

				Y.-J. Chen, M.-T. Lee, H.-C. Yao, P.-W. Hsiao, F.-C. Ke, and J.-J. Hwang Crucial Role of Estrogen Receptor-{alpha} Interaction with Transcription Coregulators in Follicle-Stimulating Hormone and Transforming Growth Factor {beta}1 Up-Regulation of Steroidogenesis in Rat Ovarian Granulosa Cells Endocrinology, September 1, 2008; 149(9): 4658 - 4668. [Abstract] [Full Text] [PDF]

				P. Kundu, A. Alioua, E. Stefani, and L. Toro Regulation of Mouse Slo Gene Expression: MULTIPLE PROMOTERS, TRANSCRIPTION START SITES, AND GENOMIC ACTION OF ESTROGEN J. Biol. Chem., September 14, 2007; 282(37): 27478 - 27492. [Abstract] [Full Text] [PDF]

				M. Moriuchi and H. Moriuchi Induction of Lactoferrin Gene Expression in Myeloid or Mammary Gland Cells by Human T-Cell Leukemia Virus Type 1 (HTLV-1) Tax: Implications for Milk-Borne Transmission of HTLV-1 J. Virol., July 15, 2006; 80(14): 7118 - 7126. [Abstract] [Full Text] [PDF]

				Z. Zhang, K. Chen, J. C. Shih, and C. T. Teng Estrogen-Related Receptors-Stimulated Monoamine Oxidase B Promoter Activity Is Down-Regulated by Estrogen Receptors Mol. Endocrinol., July 1, 2006; 20(7): 1547 - 1561. [Abstract] [Full Text] [PDF]