Pea3 transcription factor cooperates with USF-1 in regulation of the murine bax transcription without binding to an Ets-binding site

Area of Science:

• Molecular Biology
• Cell Biology
• Genetics

Background:

• The Pea3 transcription factor, part of the Ets family, plays a role in mammary gland development and cancer.
• Few target genes of Pea3 have been identified, limiting the understanding of its regulatory network.

Purpose of the Study:

• To identify novel target genes of the Pea3 transcription factor.
• To elucidate the mechanism by which Pea3 regulates the identified target gene, bax.

Main Methods:

• Pea3 overexpression and silencing in a mammary cell line.
• Reporter assays using bax promoter fragments.
• Analysis of transcription factor binding sites (Ets, E boxes).
• Co-immunoprecipitation to detect protein-DNA interactions.

Main Results:

• Bax was identified as a gene up-regulated by Pea3.
• Both Pea3 and Erm (another PEA3 group member) transactivated the bax promoter.
• The minimal bax promoter lacks an Ets-binding site but contains functional USF-1 binding sites (E boxes).
• Pea3 and USF-1 cooperate to activate the bax promoter; E box mutations reduce Pea3's transactivation potential.
• Pea3 does not directly bind the bax promoter, but USF-1 can form a ternary complex with Pea3 and DNA.

Conclusions:

• Pea3 regulates bax transcription in mammary cells.
• This regulation is mediated through cooperation with USF-1, likely without direct DNA binding by Pea3.
• The findings reveal a novel mechanism of transcriptional regulation involving Pea3 and USF-1.