title: A second estrogen receptor from Japanese lamprey (Lethenteron japonicum) does not have activities for estrogen binding and transcription.
abstract: Estrogens regulate many physiological responses in vertebrates by binding to the estrogen receptor (ER), a ligand-activated transcription factor. To understand the evolution of vertebrate ERs and to investigate how estrogen acts in a jawless vertebrate, we used degenerate primer sets and PCR to isolate DNA fragments encoding two distinct ER subtypes, Esr1a and Esr1b from the Japanese lamprey, Lethenteron japonicum. Phylogenetic analysis indicates that these two ERs are the result of lineage-specific gene duplication within the jawless fishes, different from the previous duplication event of Esr1 (ERα) and Esr2 (ERβ) within the jawed vertebrates. Reporter gene assays show that lamprey Esr1a displays both constitutive and estrogen-dependent activation of gene transcription. Domain swapping experiments indicate that constitutive activity resides in the A/B domain of lamprey Esr1a. Unexpectedly, lamprey Esr1b does not bind estradiol and is not stimulated by other estrogens, androgens or corticosteroids. A 3D model of lamprey Esr1b suggests that although estradiol fits into the steroid binding site, some stabilizing contacts between the ligand and side chains that are found in human Esr1 and Esr2 are missing in lamprey Esr1b.
authors.affiliation: Department of Biological Sciences, Hokkaido University, Sapporo, Japan; Graduate School of Life Science, Hokkaido University, Sapporo, Japan; Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, Okazaki, Japan.
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Katsu
authors.affiliation: Institute of Ecology and Evolution, University of Oregon, Eugene, OR, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Cziko
authors.affiliation: Department of Bioengineering, University of California, San Diego, CA, USA.
authors.forename: Charlie
authors.initials: C
authors.lastname: Chandsawangbhuwana
authors.affiliation: Departments of Ecology and Evolution and Human Genetics, University of Chicago, Chicago, IL, USA.
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Thornton
authors.affiliation: Graduate School of Life Science, Hokkaido University, Sapporo, Japan.
authors.forename: Rui
authors.initials: R
authors.lastname: Sato
authors.affiliation: Graduate School of Life Science, Hokkaido University, Sapporo, Japan.
authors.forename: Koari
authors.initials: K
authors.lastname: Oka
authors.affiliation: Atmosphere and Ocean Research Institute, The University of Tokyo, Chiba, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Takei
authors.affiliation: Department of Medicine, University of California, San Diego, CA, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Baker
authors.affiliation: Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, Okazaki, Japan; National Institute for Basic Biology, Okazaki, Japan. Electronic address: taisen@nibb.ac.jp.
authors.forename: Taisen
authors.initials: T
authors.lastname: Iguchi
mesh_terms: D000818:Animals; D019143:Evolution, Molecular; D006801:Humans; D007564:Japan; D007798:Lampreys / Q000235:genetics*; D010802:Phylogeny; D011960:Receptors, Estrogen / Q000235:genetics*
chemical_list: D011960:Receptors, Estrogen
keywords: Estrogen receptor; Evolution; Lamprey