Table 1. Sequences of natural EREs from estrogen-responsive genes, ER binding affinities and transcriptional activity in transfected cells.
| Name |
Sequence |
ERα binding
(Kd in nM) |
ERβ binding
(Kd in nM) |
Activation by 10 nM E2 (unless otherwise
indicated) in the given cell type |
| Xenopus vitellogenin A2 (vitERE) | 5′-GTCAGGTCACAGTGACCTGATCAAAGTTAATGTAACCTCA-3′ (19 bp ERE) | 0.2 (136); 0.39 (137); 0.31 (138); 1.2 (139); 2 (140); 1.8 (141); 1.0 (142); 2 (143); 0.8–1 (74); 10 (74); DBD alone, 1 (51) | 8 (143); ERβ binds but Kd ND (144) | 25-fold in MCF-7 (28)9.3-fold in MCF-7 transfected with ERα (136)16.7-fold in T-47D (145)5.2- and 5-fold in COS-1; 6- and 3-fold in HeLa transfected with ERα and ERβ, respectively (143)6.3-fold in CHO (142)5-fold in HeLa with 1 nM E2 (146)19-fold in HepG2 expressing ERα with 100 nM E2 (104)1.4-fold in rat calvarial osteoblast cells with 100 nM E2 (145)2.5-, 3.3- and 5-fold with ERα and 3.9, 2.6 and 3.6-fold with ERβ in CEF, HeLa and COS-1, respectively (143)30-fold in HeLa transfected with HEO ERα vector (147)17.8-fold in MCF-7 (148)4.8-fold in MCF-7 (22) |
| Chicken vitellogenin A2 | 5′-GTCCAAAGTCAGGTCACAGTGACCTGATCAAAGTT-3′ (19 bp ERE) | Ka = 80–100 µM (149) | 5-fold induction with 100 nM E2 in P19 EC (150)6-fold in HepG2 transfected with ERα with 1 µM moxestrol (151)12-fold in T-47D (152) | |
| Xenopus vitellogenin B1 | 5′-GATCTGAGTAAGTCACTGTGACCCAACCCAAGTTATGATGACC-3′ | ERα binds with ∼4.3-fold lower affinity than EREc (153) | 14.3-fold in MCF-7 with 200 nM E2 (154)3-fold induction with Xenopus ERα in Xenopus fibroblast cells (153) | |
| Xenopus vitellogenin B1 (ERE2) | 5′-GATCTGAGTAAGTCACTGTGACCTGTAAT-3′ (15 bp imperfect ERE) | 28.46 (142); DBD alone 10 (51) | 2-fold in CHO (142)No induction in Xenopus fibroblast cells (153)1.5-fold induction (102) | |
| Xenopus estrogen receptor | +480: 5′-GGTCAnnnTGACG-3′ | 10× less binding versus consensus ERE (155) | 4–5-fold (155) | |
| Chicken apo very low density lipoprotein II (apoVLDL II) | –221: 5′-GGGCTCAGTGACC-3′; then 44 bp and –178: 5′-GGTCAGACTGACC (ERE1) | ERα binds quantitatively differently to each ERE (156) | ||
| Chicken ovalbumin | –47/–43: 5′-TGGGTCA-3′ which is half ERE and an AP-1 binding site (157) | ND (158); ERα binds half-sites as a dimer with 50–100-fold lower affinity than consensus ERE (119) | ||
| Human angiotensinogen | 63-CCTGGGAACAGCTCCATCCCCACCCCTCAGCTATAAATAGGGCATCGTGACCCGGCCAGGGGA-1 | Two-tandem copies increased reporter expression (159) | ||
| Human bcl-2 | Two functional EREs: ERE-E-3 +195: 5′-GGTCGCCAGGACC-3′; ERE-E-4 + 276: 5′-GGTCCCCATGACC-3′ | ND (160) | Each gives 2.5-fold induction in MCF-7Together E-3 and E-4 give a 4-fold induction (160) | |
| Human BRCA1 | +2023: 5′-TGGTCAGGCTGGTCTGGAACTCCTGACCTG -3′ | ND | ND | 10 nM E2 induces 1.5-fold increase in MCF-7 (105) |
| Human calbindin-D9k | 5′-GATCCAGGTTAGTGTGATTTG-3′ | No binding (161) | ||
| Human cathepsin D | (–270 to –249) 5′-GGGCCGGGCTGACCCCGCGGG-3′ (called the E2 site) | 3 (136) 136 nM at 200 mM KCl (108) | Lower apparent affinity of ERβ versus ERα (144) | 0.6-fold in MCF-7 transfected with ERα (136) |
| Human choline acetyltransferase | 5′-GATCCAGGAGGCCACGATGACATGCTC-3′ | ND (144) | Lower apparent affinity of ERβ versus ERα (144) | |
| Human complement C3 | –236: 5′-GTGTTCACCAGGTGGCCCTGACCCTGGGAG-AGTCCA-3′; +25: 5′-TGTCCCTCTGTCCCTCTGACCCTGCACTGTCC-CAGCAACCATG(start)-3′; for EMSA: 5′-CACCAGGTGGCCCTGACC-3′ (162) | ERα bound, but not all supershifted with ERα antibody, Kd ND (162) | 5.6-fold in HepG2, 4-fold in HeLa and 10-fold in T47D transfected with ERα (162)2-fold in MCF-7 (22)The –240 ERE is functional, but the +33 ERE is not (162) | |
| Human cytochrome c oxidase subunit VIIa-related protein (COX7RP) | + 443 (intron): 5′-TCACTGCAGGGGTCAAGGTGACCCCCGGGGTCA-3′ | ERα binding identical to vitERE (163) | 6-fold induction with 100 nM E2 in MCF-7 (163) | |
| Human ERβ | –1510: 5′-TGGTCAGGCTGGTC(N9)TGACC-3′ | ND (106) | ND (106) | |
| Human estrogen responsive finger protein (efp) | 3′ non-coding region: 5′-TTCAGGGTCATGGTGACCCTGAT-3′ | ND (164–166) | ||
| Human Ha-ras Exon1 | +1713: 5′-GCGCTGACCATCCAGCTGATCCAGAACC-3′ | ND (167) | 3.7-fold increase in MCF-7 (167) | |
| Human hepatic α2u globulin | –606: 5′-GATCCAAAAGAGGGTCATTTCCTGTGACTGGAG-3′ | ND (168) | Negatively regulated by E2 (168–171) | |
| Human lactoferrin | –374: 5′-AAGAAGATAGCAGGTCAAGGCGATCTGTAAAGACCCTCTGCTCT-3′ | 6.5-fold in RL-95-2 cells (172)7-fold in HEC-1B transfected with ERα (57) | ||
| Human progesterone receptor (hPR) | Form B is initiated at +744: +540: 5′-ATGGAGGCCAAGGGCAGGAGCTGACCAGCGCCGCCCT-3′ Form A is initiated at + 1236: +1148: 5′-TCCTGCGAGGTCACCAGCTCTTGGT-3′ (173) | ‘Weak but detectable’ (174) | Induction equal to vitERE in COS-7 transfected with ERα (164) | |
| +565: AGGAGCTGACCAGCGCCGCCCTCCCCCGCCCCCGACC-3′ | Foot-prints (175) | 1.7-fold in CHO transfected with ERα (175) | ||
| Human quinone reductase | –476: 5′-AATTAAATCGCAGTCACAGTGACTCAGCAGAATCTGAGCCTAGG-3′ | ND (176) | ERβ binds, Kd ND (176) | E2 does not induce4-OHT activates 2- and 4-fold induction in HEC-1 transfected with ERα and ERβ, respectively (176) |
| Human pS2 | 5′-CTTCCCCCTGCAAGGTCAGCGTGGCCACCCCGTGAGCCACT-3′ | 0.40 (E2) and 1.14 (no ligand) (138); 22.1 (142) | ERβ binds but Kd ND (144) | 4.5-fold in HeLa transfected with HEO ERα vector (147)2.5-fold in CHO (142) |
| Human VEGF | –1560: 5′-AATCAGACTGACTGGCCTCAGAGCC-3′ | ND (177) | Two tandem copies give a 4.2-fold increase with 100 nM E2 in Ishikawa cells transfected with ERα (177) | |
| Human genome Alu ERE | 5′-TGGTCAGGCTGGTCTCAAACTCCTGACCTCGTGATCTCA-3′ | 100 nM E2 activates 8-fold induction in HepG2 (178) | ||
| Rat calbindin-D9k | 5′-GATCCAGGTCAGGGTGATCTG-3′ | ND (161,179) | ||
| Rat creatine kinase B | –569: 5′-GGGAAGGTCAGAACACCCTGGGTGCTTCCCC-3′ | ND (180) | 7-fold in HeLa (180)8-fold induction in ECC-1 (181) | |
| Rat hsp70-related gene | 5′-GGTCACTCCGACC-3′ | Not estrogen responsive (182,183) | ||
| Rat luteinizing hormone B | 5′-TCACATGGACACCATCTGTCCCGATCGGCTCCAAGGTTACATTGACCAC-3′ | ND (184) | 2.5-fold in GH3 cells (184) | |
| Rat c-jun | +1021 (exon): 5′-CTGAAGCAGAGCATGACCTTGAACTGAAGCAGAGCATGACCTTGAA-3′ | 10–20 (148) | ERβ binds; Kd ND (144) | 2.7-fold in H301 cells (148) |
| Rat c-jun (JUN5) | 5′-GATCCTGAAGCAGAGCATGACCTTGAA-3′ | No direct binding, but competed for ERα–vitERE binding (185) | 4-fold induction in a yeast reporter assay (185) | |
| Rat oxytocin | (–115 to –85) 5′-AGTGTGGAACAGTTTGACCCAAGAGACCTGCTGTGACCA-3′ C-3′ (imperfect 13 bp ERE)(–147 to –177): 5′-GATCCAGGCGGTGACCTTGACCCCAGC-3′ | 8-fold with 100 nM E2 in P19 EC cells (150) | ||
| Rat prolactin | –1713: 5′-TCCAGGTCACCAGCTGCTTCAGATGATC-3′ | 70 (188) | No effect of E2 (189) | |
| –1573: 5′-GATCCTTGTCACTATGTCCTAGAGTGGATC-3′ (186,187) | 602 (188) | |||
| –1547: 5′-AGCTATAGATCATGAGGTCATAACGATTTATG-3′ | ND (59,188) | |||
| –1786: 5′-AGCTAGAACCAGGTCATCTGTCAGTCCAAATG-3′ –1573: 5′-AGCTGCTTTGGGGTCAGAAGAGGCAGGCAGAG-3′ | ||||
| Rat vasopressin | –4324: 5′-TGCTTCTGCAGGGCCAGCCTGACCGTGTGT-3′ | ND (190) | ND (190) | E2–ERα induces 1.6-fold; E2–ERβ induces 1.3-fold500 nM 4-OHT- ERα induces 2.9-fold; 500 nM ICI 182,780-ERα induces 3.4-fold (190) |
| Rat VEGF5′ | VEGF5′ between TATA box and +1: +: 5′-GATCGACAGGGCAAAGTGACTGACCT-3′ | ERα < ERβ binding (191) | Two tandem copies in the forward orientation inhibit ERα activity by >50%, but show a 2-fold induction if cloned in reverse orientation. Two tandem copies in the forward orientation are inactive with ERβ, but show 2-fold activation with ERβ if cloned in reverse orientation; however ICI 182,780 doesn’t block E2–ERβ activity. This is the first report of an orientation-dependent effect on ERα transcription (191). | |
| Rat VEGF3′ | In 3′UTR: 5′-GATCTGCAAGAGCACCCTGCCCTCTGG-3′ | Binding of ERα and ERβ is approximately equal (191) | Two tandem copies give 3- and 1.5-fold increase with ERα and ERβ, respectively, in transfected HeLa (191) | |
| Mouse c-fos | –278: 5′-GCGGAAGGTCTAGGAGACCCCCTAG-3′ | ND | ERβ binds; Kd ND (144) | 2–5-fold (192) |
| 3′ to gene: 5′-TTTATCCAGGTCACCACAGCCCAGGCCATG-3′ | 1–10 (148) | 4.5-fold (148) | ||
| Mouse oviduct-specific glyoprotein | –115: 5′-GTCAGCGGTCATTGTGATCTTGAATCATTGTTTCT-3′ | ND (193) | 2.5-fold in MCF-7 cells treated with 100 nM E2 (193) | |
| Rabbit uteroglobin | –275: 5′-GCAGGTGGCCAGGTCACCATGCCCTCGGGGGGCAGGCACC-3′ | ND (194); 3–4-fold < vitERE (195) | 7-fold in Ishikawa (195)Role for Sp1 (7) | |
| Guinea pig estrogen sulfotransferase gene 2 | –2442: 5′-AGGTCATCCAACCA-3′ –982: 5′-AGGTCATGTTGTTC-3′ | ND (196) |
The species and gene name are indicated. The underlined nucleotides constitute the consensus ERE half-site sequence and nucleotides in bold type are altered from the consensus ERE palindrome.
ND, not determined.