Major Egr3 Isoforms Are Generated via Alternate Translation Start Sites and Differ in Their Abilities To Activate Transcription

Abstract

In previous studies, we detected a major, unidentified Egr response element (ERE) binding complex in brain extracts. We now report that this complex contains a truncated isoform of Egr3 generated by use of an alternate translation start site at methionine 106. Furthermore, the ERE binding complex previously thought to contain full-length Egr3 includes several isoforms generated by initiation at other internal methionines. Full-length and truncated (missing residues 1 to 105) Egr3 isoforms differ in the ability to stimulate transcription directed by a tandem repeat of two EREs but not by a single ERE. Taken together, our results indicate that alternative translation start sites are used to generate Egr3 isoforms with distinct transcriptional properties.

ACKNOWLEDGMENTS

This study was supported by Public Health Service grants from the National Institute of Drug Abuse (DA00266 and DA00358 [J.M.B.] and DA05753 [K.J.O.]) and an NARSAD independent investigator award (J.M.B.).

We thank E. Eipper, D. Ginty, S. S. Wang, and P. Worley for use of equipment, helpful discussions, and advice; D. Ahn, Y. S. Kwon, and W. Z. Tang for expert technical assistance; Jeff Milbrandt and Warren Tourtellotte for generously providing reagents and samples; and D. Ginty for critical reading of the manuscript.