Ligand-dependent transcriptional enhancement by DNA curvature between two half motifs of the estrogen response element in the human estrogen receptor alpha gene

We previously reported five DNA bend sites (ERB-4 to -1, and ERB+1) in the promoter region of the human estrogen receptor alpha (ERalpha) gene [FEBS Lett. 444 (1999) 117]. One of these sites, ERB-2, was accompanied by two half motifs of the estrogen response element (ERE) and several short poly(dA)(...

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Published in:Gene 2002-07, Vol.294 (1-2), p.279-290
Main Authors: Li, Xiao-man, Onishi, Yoshiaki, Kuwabara, Kentaro, Rho, Jeung-yon, Wada-Kiyama, Yuko, Sakuma, Yasuo, Kiyama, Ryoiti
Format: Article
Language:English
Subjects:
Base Sequence
Binding Sites - genetics
Binding, Competitive
DNA - chemistry
DNA - genetics
DNA - metabolism
DNA Methylation
Estrogen Receptor alpha
Estrogens - metabolism
Estrogens - pharmacology
Humans
Ligands
Molecular Sequence Data
Mutation
Nucleic Acid Conformation
Oligonucleotides - genetics
Oligonucleotides - metabolism
Promoter Regions, Genetic - genetics
Protein Binding
Receptors, Estrogen - genetics
Receptors, Estrogen - metabolism
Response Elements - genetics
Sequence Homology, Nucleic Acid
Transcriptional Activation - drug effects
Tumor Cells, Cultured
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Summary:We previously reported five DNA bend sites (ERB-4 to -1, and ERB+1) in the promoter region of the human estrogen receptor alpha (ERalpha) gene [FEBS Lett. 444 (1999) 117]. One of these sites, ERB-2, was accompanied by two half motifs of the estrogen response element (ERE) and several short poly(dA)(.)poly(dT) tracts including an A(4) tract located next to a half ERE motif. This A(4) tract and the 20 bp immediate flanking sequence containing a half ERE motif (T3B) exhibited DNA curvature. Transcription assays using luciferase as a reporter gene indicated that T3B sequence conferred positive estrogen responsiveness. Mutations introduced in this sequence indicated that both bendability and estrogen responsiveness were synergistically associated with the A(4) tract located next to the half ERE motif. This motif and a mutant sequence, GGTTA, had affinity for ERalpha protein, which seems to account for ERalpha protein binding to the region without an ERE motif. These findings suggest that some DNA curvature acts as a transcriptional modulator by modifying the state of ligand effects.
ISSN:0378-1119
DOI:10.1016/S0378-1119(02)00803-X