RT Journal
A1 Lim, Hee-Woong
A1 Uhlenhaut, N. Henriette
A1 Rauch, Alexander
A1 Weiner, Juliane
A1 Hübner, Sabine
A1 Hübner, Norbert
A1 Won, Kyoung-Jae
A1 Lazar, Mitchell A.
A1 Tuckermann, Jan
A1 Steger, David J.
T1 Genomic redistribution of GR monomers and dimers mediates transcriptional response to exogenous glucocorticoid in vivo
JF Genome Research 
JO Genome Research 
YR 2015 
FD June 01 
VO 25 
IS 6 
SP 836 
OP 844 
DO 10.1101/gr.188581.114 
UL http://genome.cshlp.org/content/25/6/836.abstract 
AB Glucocorticoids (GCs) are commonly prescribed drugs, but their anti-inflammatory benefits are mitigated by metabolic side effects. Their transcriptional effects, including tissue-specific gene activation and repression, are mediated by the glucocorticoid receptor (GR), which is known to bind as a homodimer to a palindromic DNA sequence. Using ChIP-exo in mouse liver under endogenous corticosterone exposure, we report here that monomeric GR interaction with a half-site motif is more prevalent than homodimer binding. Monomers colocalize with lineage-determining transcription factors in both liver and primary macrophages, and the GR half-site motif drives transcription, suggesting that monomeric binding is fundamental to GR's tissue-specific functions. In response to exogenous GC in vivo, GR dimers assemble on chromatin near ligand-activated genes, concomitant with monomer evacuation of sites near repressed genes. Thus, pharmacological GCs mediate gene expression by favoring GR homodimer occupancy at classic palindromic sites at the expense of monomeric binding. The findings have important implications for improving therapies that target GR.