The ERR-1 orphan receptor is a transcriptional activator expressed during bone development.
We studied the expression of estrogen-related receptor ERR-1 during mouse embryonic development. ERR-1 mRNA is present in bones formed by both the endochondral and intramembranous routes, and the onset of its expression coincides with bone formation. By RT-PCR experiments, we found that ERR-1, but not the related receptor ERR-2, is expressed in osteoblastic osteosarcoma cell lines as well as in primary osteoblastic cell populations derived from normal human bone. By gel shift analysis we found that ERR-1 binds as a monomer specifically to the SFRE sequence (SF-1-responsive-element; TCAAGGTCA). Mutation analysis revealed that both the core AGGTCA motif and the TCA 5'-extension are required for efficient ERR-1 binding. In transient transfection assays, ERR-1 acts as a potent transactivator through the SFRE sequence. This effect is cell-specific since ERR-1 activates transcription in the rat osteosarcoma cell line ROS 17.2/8 as well as in HeLa, NB-E, and FREJ4 cells but not in COS1 and HepG2 cells. Notably, the osteopontin (a protein expressed by osteoblasts and released in the bone matrix) gene promoter is a target for ERR-1 transcriptional regulation. Our findings suggest a role for ERR-1 in bone development and metabolism.
Bonnelye
E
E
CNRS UMR 319, Mécanismes du développement et de la Cancérisation, Institut de Biologie de Lille, France.
Vanacker
J M
JM
Dittmar
T
T
Begue
A
A
Desbiens
X
X
Denhardt
D T
DT
Aubin
J E
JE
Laudet
V
V
Fournier
B
B
D000818:Animals; D001483:Base Sequence; D001846:Bone Development / Q000235:genetics*; D001842:Bone and Bones / Q000196:embryology* / Q000378:metabolism; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000737:chemistry; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D017403:In Situ Hybridization; D051379:Mice; D016133:Polymerase Chain Reaction; D011485:Protein Binding / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics* / Q000378:metabolism; D017421:Sequence Analysis; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation / Q000235:genetics*; D000097983:ERRalpha Estrogen-Related Receptor
D004247:DNA; D017931:DNA Primers; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen; D014157:Transcription Factors; D000097983:ERRalpha Estrogen-Related Receptor; C490918:ESRRB protein, human; C098925:Esrrb protein, mouse