The tri-nucleotide spacer sequence between estrogen response element half-sites is conserved and modulates ERalpha-mediated transcriptional responses.

ABSTRACT: The estrogen response element (ERE) consensus sequence is AGGTCAnnnTGACCT, where nnn is known as the tri-nucleotide spacer sequence. Studying 1017 high-confidence ERalpha-bound loci, we found that genomic EREs are enriched for spacers composed of C(A/T)G, suggesting that the spacer may influence receptor binding and transcriptional responses. We designed consensus EREs containing variable spacer sequences and compared ERalpha binding in gel shift assays and enhancer function in reporter assays. We found that ERalpha-ERE binding affinity is modulated by the tri-nucleotide spacer sequence and is favored by spacer sequences of CTG>GCC>TTT. Similarly, luciferase reporter assays indicated that the estrogen-stimulated transcriptional response is modulated by the spacer and parallels the gel shif

SUBMITTER: Shu FJ 

PROVIDER: S-EPMC2891080 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature