The ERR-1 orphan receptor is a transcriptional activator expressed during bone development

Mol Endocrinol. 1997 Jun;11(7):905-16. doi: 10.1210/mend.11.7.9948.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Bone Development / genetics*
  • Bone and Bones / embryology*
  • Bone and Bones / metabolism
  • Cell Line
  • DNA / metabolism
  • DNA Primers / chemistry
  • Embryo, Mammalian / anatomy & histology
  • Embryo, Mammalian / chemistry
  • Gene Expression Regulation, Developmental / genetics*
  • In Situ Hybridization
  • Mice
  • Polymerase Chain Reaction
  • Protein Binding / genetics
  • Receptors, Cytoplasmic and Nuclear / genetics*
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Receptors, Estrogen / genetics*
  • Receptors, Estrogen / metabolism
  • Sequence Analysis
  • Transcription Factors / metabolism*
  • Transcriptional Activation / genetics*


  • DNA Primers
  • ERRalpha estrogen-related receptor
  • ESRRB protein, human
  • Esrrb protein, mouse
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Estrogen
  • Transcription Factors
  • DNA