Effects of wild type and mutant estrogen receptors on DNA flexibility, DNA bending, and transcription activation

Sara J. Potthoff, Lorene E. Romine, Ann M. Nardulli

Research output: Contribution to journalArticlepeer-review


We examined the ability of wild type (WT) estrogen receptor (ER) and mutant ERs to induce distortion and directed bends in DNA fragments containing estrogen response elements and then monitored the ability of these receptors to activate transcription. The ER mutants had either 108 (109-595 ER) or 175 (ΔAB ER) amino acids deleted from the amino terminus; 42 (ΔF ER) or 65 (1-530 ER) amino acids deleted from the carboxy terminus; or a single point mutation at amino acid 380 (glu→gln) in the ER hormone binding domain (E380Q ER). Circular permutation analysis was used to determine the degree of distortion induced in estrogen response element-containing DNA fragments (65° for WT ER and E380Q ER, 56° for 109-595 ER, 54° for ΔAB ER, 63° for ΔF ER, and 60° for 1-530 ER). Phasing analysis delineated the magnitude of directed DNA bends (8.3° for WT ER, 6.9° for 109-595 ER, 6.5° for ΔAB ER, 10.6° for ΔF ER, 12.4° for 1-530 ER, and 10.2° for E380Q ER) and demonstrated that the direction of the bend was always toward the major groove of the DNA helix. The ability of each receptor to induce transcription of an estrogen-responsive reporter plasmid (E380Q ER>WT ER=ΔF ER>109-595 ER> ΔAB ER>1-530 ER) was related to the ability of the receptor to induce appropriate distortion (63°-65°) and directed DNA bending (8°-10°) angles and the presence of transcription activation functions AF-1 and AF-2. These studies suggest that ER-induced DNA bending is one part of a multistep process involved in regulating estrogen-responsive genes.

Original languageEnglish (US)
Pages (from-to)1095-1106
Number of pages12
JournalMolecular Endocrinology
Issue number9
StatePublished - 1996

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology


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