Comparison of transcriptional synergy of estrogen receptors Î± and Î² from multiple tandem estrogen response elements

Tyulmenkov, Valentyn V.

doi:10.1016/s0303-7207(00)00250-1

Cited by 40 publications

(26 citation statements)

References 38 publications

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“…On the other hand, hERβ expression slightly inhibited the endogenous response of Ishikawa(+) cells (Figure 2A). This phenomenon is consistent with what other laboratories have reported and is a result of the difference in endogenous ER expression (70)(71)(72)(73). The endogenous low ERβ expression was unable to transmit an estrogenic response ( Figure 2B).…”

Section: Resultssupporting

confidence: 93%

DDT and its metabolites alter gene expression in human uterine cell lines through estrogen receptor-independent mechanisms.

Frigo

Burow

Mitchell

et al. 2002

Environ Health Perspect

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Endocrine-disrupting organochlorines, such as the pesticide dichlorodiphenyltrichloroethane (DDT), bind to and activate estrogen receptors (ERs), thereby eliciting estrogen-like effects. Although ERs function predominantly through activation of transcription via estrogen-responsive elements, both ERs, alpha and ss, can interact with various transcription factors such as activator protein-1 (AP-1). Additionally, estrogens may regulate early signaling events, suggesting that the biological effects of environmental estrogens may not be mediated through classic ER (alpha and ss) activity alone. We hypothesized that known environmental estrogens, such as DDT and its metabolites, activate AP-1-mediated gene transactivation through both ER-dependent and ER-independent means. Using two Ishikawa human endometrial adenocarcinoma cell line variants that we confirmed to be estrogen responsive [Ishikawa(+)] and estrogen unresponsive [Ishikawa(-)], we generated stably transfected AP-1 luciferase cell lines to identify the role of an estrogen-responsive mechanism in AP-1-mediated gene expression by various stimuli. Our results demonstrate that DDT and dichlorodiphenyldichloroethane (DDD) were the most potent activators of AP-1 activity; 2,2-bis(p-chlorophenyl) acetic acid failed to activate. Although stimulated in both Ishikawa(+) and Ishikawa(-) cells by DDT and its congeners, AP-1 activation was more pronounced in the estrogen-unresponsive Ishikawa(-) cells. In addition, DDT, DDD, and dichlorodiphenyldichloroethylene (DDE) could also stimulate AP-1 activity in the estrogen-unresponsive human embryonic kidney 293 cells using a different promoter context. Thus, our data demonstrate that DDT and its metabolites activate the AP-1 transcription factor independent of ER (alpha or ss) status.

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Section: Resultssupporting

confidence: 93%

DDT and its metabolites alter gene expression in human uterine cell lines through estrogen receptor-independent mechanisms.

Frigo

Burow

Mitchell

et al. 2002

Environ Health Perspect

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“…We reported a correlation between the apparent binding affinity (K d ) of ER binding to specific ERE sequences, as determined by EMSA, and E 2 -induced transactivation potential in transient transfection experiments (Klinge et al 1992b, 1996a, Tyulmenkov et al 2000. As anticipated, a trypsin concentration-dependent loss of intact ER was detected for both E 2 -and 4-OHT-occupied ER bound to pS2 (Fig.…”

Section: Comparison Of Er Digestion When Incubated With Erec38 Vs Ps2supporting

confidence: 55%

“…Multiple copies of EREc38 cloned head-to-tail as a tandem array demonstrated cooperative E 2 -ER binding and synergistic transactivation potential (Tyulmenkov et al 2000). This result, combined with the data showing that binding to 1 EREc38 enhanced trypsin digestion of ER ( Fig.…”

Section: Effect Of Multiple Tandem Copies Of Erec38 On Sensitivity Ofsupporting

confidence: 54%

“…Apparent equilibrium dissociation constants (K d ) were calculated from electrophoretic mobility shift assay (EMSA) data using a one-site competition model (GraphPad Prism, v.3) (Tyulmenkov et al 2000). These values and the mean luciferase activities from transfection experiments were dichotomized using the criteria described in the text and organized in 2 2 contingency tables to employ chi-square independence tests in Microsoft Excel 97.…”

Section: Other Statistical Treatmentsmentioning

confidence: 99%

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Estrogen response element binding induces alterations in estrogen receptor-alpha conformation as revealed by susceptibility to partial proteolysis

Ramsey

Klinge

2001

Journal of Molecular Endocrinology

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Genes whose expression is highly induced by estradiol (E 2 ) contain multiple estrogen response elements (EREs) in their promoters. Previously we reported that estrogen receptor-(ER ) binds cooperatively to and E 2 synergistically activates reporter gene expression from three or four tandem copies of a consensus ERE (EREc38). Here we evaluated how ER binding to one, two, three or four tandem copies of EREc38 affects ER conformation as detected by altered ER trypsin digestion patterns in Western blots. E 2 -or 4-hydroxytamoxifen (4-OHT)-occupied ER bound to the pS2 ERE or to a single copy of EREc38 showed enhanced susceptibility to trypsin digestion compared to E 2 -or 4-OHT-ER incubated with DNA lacking an ERE. ER binding to multiple tandem copies of EREc38 further increased sensitivity to trypsin digestion. These results correlate with synergistic transcription and cooperativity of ER binding to multiple tandem copies of EREc38. These observations suggest that EREc38 binding alters the overall conformation of ER and that multiple tandem copies of EREc38 enhance these conformational changes. We hypothesize that EREinduced alterations in ER conformation modulate interaction with coregulatory proteins, resulting in synergistic transcriptional activation.

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“…Multiple copies of EREs also influence the estrogen response of a target gene. Electrophoretic mobility shift assay (EMSA) studies of ER binding to three or four tandem repeats of the ERE suggested that receptor binding is stabilized by dimers at adjacent sites and this cooperative binding promotes transcriptional synergy (Tyulmenkov et al 2000).…”

Section: Introductionmentioning

confidence: 99%

Estrogen response element and the promoter context of the human and mouse lactoferrin genes influence estrogen receptor α-mediated transactivation activity in mammary gland cells

Stokes

Alston-Mills²,

Teng

2004

Journal of Molecular Endocrinology

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A critical step in estrogen action is the recognition of estrogen responsive elements (EREs) by liganded estrogen receptor. Our current studies were designed to determine whether an extended estrogen response element half-site (ERRE) contributes to the differential estrogen responses of the human and mouse lactoferrin overlapping chicken ovalbumin upstream promoter/ERE sequences (estrogen response modules, ERMs) in the context of their natural promoters. Transient transfections of MCF-7 cells show that liganded estrogen receptor (ER ) activates transcription of the human lactoferrin ERM fourfold higher than the mouse lactoferrin ERM in the context of their natural promoters. Since the ERRE of the human lactoferrin gene naturally occurs 18 bp upstream from the ERM and is absent in the mouse lactoferrin gene promoter, we created a chimeric mouse lactoferrin CAT reporter, which now encodes the ERRE in the identical location as in the human lactoferrin gene. The addition of the ERRE in the mouse lactoferrin gene rendered this reporter extremely responsive to estrogen stimulation. Using limited protease digestions and electrophoretic mobility shift assays, we showed that the binding and protease sensitivity of ER bound to the mouse ERM with or without the ERRE, differed. Importantly, occupancy of additional nuclear receptors at the ERRE may contribute to ER binding and activation. Furthermore, the presence of ERRE influences the selectivity of coactivators in liganded ER -mediated transcriptional activity. When the receptor is bound to human and mouse plus genes, which contain the ERRE, steroid receptor coactivator (SRC)-2 was preferred, while SRC-1 and SRC-3 coactivators selectively enhanced the mouse lactoferrin gene activity. Moreover, peroxisome proliferator activated receptor-coactivator-1 (PGC-1 ) and PGC-1-related estrogen receptor coactivator (PERC) robustly increase the transcriptional function of ER in the presence of the ERRE. In conclusion, these data show that the context of the lactoferrin gene influences the ER -mediated transcriptional activity.

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Comparison of transcriptional synergy of estrogen receptors Î± and Î² from multiple tandem estrogen response elements

Cited by 40 publications

References 38 publications

DDT and its metabolites alter gene expression in human uterine cell lines through estrogen receptor-independent mechanisms.

DDT and its metabolites alter gene expression in human uterine cell lines through estrogen receptor-independent mechanisms.

Estrogen response element binding induces alterations in estrogen receptor-alpha conformation as revealed by susceptibility to partial proteolysis

Estrogen response element and the promoter context of the human and mouse lactoferrin genes influence estrogen receptor α-mediated transactivation activity in mammary gland cells

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