The protooncogene c-jun contains an unusual estrogen-inducible enhancer within the coding sequence

Area of Science:

• Molecular Biology
• Endocrinology
• Oncology

Background:

• Estrogens are known to increase c-jun mRNA levels, indicating a role in hormone-induced cell proliferation.
• This process is primarily mediated by transcriptional activation, a fundamental mechanism in gene regulation.

Purpose of the Study:

• To identify and characterize the specific estrogen-dependent regulatory element within the c-jun gene.
• To elucidate the mechanism by which estrogen receptor interacts with this element to control c-jun transcription.

Main Methods:

• Sequence analysis to identify potential estrogen response elements (EREs) within the c-jun gene.
• Electrophoretic mobility shift assays (EMSAs) to assess estrogen receptor binding to the identified jun sequence.
• Reporter gene assays in yeast and mammalian cells to evaluate transcriptional activity.

Main Results:

• An estrogen-dependent enhancer with a unique sequence (GCAGAnnnTGACC) was identified within the c-jun coding sequence.
• The identified jun sequence binds the estrogen receptor, although it differs from the consensus ERE in the first half-site.
• Both half-sites of the jun element are crucial for hormone-inducible transcriptional activation, while only the TGACC half-site is essential for receptor binding.

Conclusions:

• Estrogen receptor binds as a heterodimer to regulate c-jun protooncogene transcription.
• AP-1 components, including c-jun, function as early response genes in estrogen-induced proliferation, linking hormonal signaling to cell growth.