Publication
Title
Inhibition of Corticosteroid-Binding Globulin Gene Expression by Glucocorticoids Involves C/EBP beta
Author
Abstract
Corticosteroid-binding globulin (CBG), a negative acute phase protein produced primarily in the liver, is responsible for the transport of glucocorticoids (GCs). It also modulates the bioavailability of GCs, as only free or unbound steroids are biologically active. Fluctuations in CBG levels therefore can directly affect GC bioavailability. This study investigates the molecular mechanism whereby GCs inhibit the expression of CBG. GCs regulate gene expression via the glucocorticoid receptor (GR), which either directly binds to DNA or acts indirectly via tethering to other DNA-bound transcription factors. Although no GC-response elements (GRE) are present in the Cbg promoter, putative binding sites for C/EBP beta, able to tether to the GR, as well as HNF3 alpha involved in GR signaling, are present. C/EBP beta, but not HNF3 alpha, was identified as an important mediator of DEX-mediated inhibition of Cbg promoter activity by using specific deletion and mutant promoter reporter constructs of Cbg. Furthermore, knockdown of C/EBP beta protein expression reduced DEX-induced repression of CBG mRNA, confirming C/EBP beta's involvement in GC-mediated CBG repression. Chromatin immunoprecipitation (ChIP) after DEX treatment indicated increased co-recruitment of C/EBP beta and GR to the Cbg promoter, while C/EBP beta knockdown prevented GR recruitment. Together, the results suggest that DEX repression of CBG involves tethering of the GR to C/EBP beta.
Language
English
Source (journal)
PLoS ONE
Publication
2014
ISSN
1932-6203
Volume/pages
9:10(2014), 14 p.
Article Reference
e110702
ISI
000343731200069
Medium
E-only publicatie
Full text (Publisher's DOI)
Full text (open access)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 10.12.2014
Last edited 04.10.2017
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