skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Tethering not required: the glucocorticoid receptor binds directly to activator protein-1 recognition motifs to repress inflammatory genes

Authors:
; ; ; ; ; ; ORCiD logo
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
NIHOTHER
OSTI Identifier:
1393653
Resource Type:
Journal Article
Resource Relation:
Journal Name: Nucleic Acids Research; Journal Volume: 45; Journal Issue: 14
Country of Publication:
United States
Language:
ENGLISH

Citation Formats

Weikum, Emily R., de Vera, Ian Mitchelle S., Nwachukwu, Jerome C., Hudson, William H., Nettles, Kendall W., Kojetin, Douglas J., and Ortlund, Eric A. Tethering not required: the glucocorticoid receptor binds directly to activator protein-1 recognition motifs to repress inflammatory genes. United States: N. p., 2017. Web. doi:10.1093/nar/gkx509.
Weikum, Emily R., de Vera, Ian Mitchelle S., Nwachukwu, Jerome C., Hudson, William H., Nettles, Kendall W., Kojetin, Douglas J., & Ortlund, Eric A. Tethering not required: the glucocorticoid receptor binds directly to activator protein-1 recognition motifs to repress inflammatory genes. United States. doi:10.1093/nar/gkx509.
Weikum, Emily R., de Vera, Ian Mitchelle S., Nwachukwu, Jerome C., Hudson, William H., Nettles, Kendall W., Kojetin, Douglas J., and Ortlund, Eric A. Wed . "Tethering not required: the glucocorticoid receptor binds directly to activator protein-1 recognition motifs to repress inflammatory genes". United States. doi:10.1093/nar/gkx509.
@article{osti_1393653,
title = {Tethering not required: the glucocorticoid receptor binds directly to activator protein-1 recognition motifs to repress inflammatory genes},
author = {Weikum, Emily R. and de Vera, Ian Mitchelle S. and Nwachukwu, Jerome C. and Hudson, William H. and Nettles, Kendall W. and Kojetin, Douglas J. and Ortlund, Eric A.},
abstractNote = {},
doi = {10.1093/nar/gkx509},
journal = {Nucleic Acids Research},
number = 14,
volume = 45,
place = {United States},
year = {Wed Jun 07 00:00:00 EDT 2017},
month = {Wed Jun 07 00:00:00 EDT 2017}
}
  • Macrophage inflammatory protein-1{alpha} (MIP-1{alpha}) and RANTES are members of the {beta} chemokine family of leukocyte chemoattractants. We have previously cloned three mouse genes by cross-hybridization with the human MIP-1{alpha}/RANTES receptor gene CMKBR1. One of the mouse genes, Scya3r, encodes a functional MIP-1{alpha} receptor. The functions of the other two, Scya3r-rs1 and Scya3r-rs2, are not known. We have now mapped Scya3r, Scya3r-rs1, and Scya3r-rs2 to chromosome 9, in a region of conserved synteny with the location of CMKBR1. Thus, like chemokine genes and {alpha} chemokine receptor genes, this group of {Beta} chemokine receptor genes arose by tandem duplication. 17 refs., 2more » figs.« less
  • The complex of the rat glucocorticoid receptor (GR) DNA binding domain (DBD) and half-site sequence of the consensus glucocorticoid response element (GRE) has been studied by two-dimensional {sup 1}H NMR spectroscopy. The DNA fragment is a 10 base-pair oligonucleotide, 5{prime}d(GCTGTTCTGC)3{prime}{center dot}5{prime}d-(GCAGAACAGC)3{prime}, containing the stronger binding GRE half-site hexamer, with GC base pairs at each end. The 93-residue GR-DBD contains an 86-residue segment corresponding to residues 440-525 of the rat GR. Eleven NOE cross peaks between the protein and DNA have been identified, and changes in the chemical shift of the DNA protons upon complex formation have been analyzed. Using thesemore » protein-DNA contact points, it can be concluded that (1) the 'recognition helix' formed by residues C460-E469 lies in the major groove of the DNA; (2) the GR-DBD is oriented on the GRE half-site such that residues A477-D481, forming the so-called D-loop, are available for protein-protein interaction in the GR-DBD dimer on the intact consensus GRE; and (3) the 5-methyl of the second thymine in the half-site and valine 462 interact, confirming indirect evidence that both play an important role in GR-DBD DNA binding.« less
  • No abstract prepared.
  • Expression of the human osteocalcin promoter is negatively regulated by glucocorticoids in vivo. In vitro DNase I and exonuclease III footprinting analysis showed binding of purified glucocorticoid receptor in close proximity to and overlapping with the TATA box of the osteocalcin gene. These results imply competition or interference with binding of the TATA box-binding transcription factor IID as a mechanism of repression of this gene by glucocorticoids. In support of this notion, point mutation analysis of the receptor binding site indicated that flanking nucleotides and not the TATA box motif per se were important for receptor interaction. Moreover, DNA bindingmore » competition assays showed specific binding of the receptor only to the TATA box region of the osteocalcin gene and not to the corresponding region of an immunoglobulin heavy-chain promoter.« less