PMID- 10430878
OWN - NLM
STAT- MEDLINE
DCOM- 19990909
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 16
DP  - 1999 Aug 3
TI  - Antiglucocorticoid activity of hepatocyte nuclear factor-6.
PG  - 8961-6
AB  - Glucocorticoids exert their effects on gene transcription through ubiquitous
      receptors that bind to regulatory sequences present in many genes. These
      glucocorticoid receptors are present in all cell types, yet glucocorticoid action
      is controlled in a tissue-specific way. One mechanism for this control relies on 
      tissue-specific transcriptional activators that bind in the vicinity of the
      glucocorticoid receptor and are required for receptor action. We now describe a
      gene-specific and tissue-specific inhibitory mechanism through which
      glucocorticoid action is repressed by a tissue-restricted transcription factor,
      hepatocyte nuclear factor-6 (HNF-6). HNF-6 inhibits the glucocorticoid-induced
      stimulation of two genes coding for enzymes of liver glucose metabolism, namely
      6-phosphofructo-2-kinase and phosphoenolpyruvate carboxykinase. Binding of HNF-6 
      to DNA is required for inhibition of glucocorticoid receptor activity. In vitro
      and in vivo experiments suggest that this inhibition is mediated by a direct
      HNF-6/glucocorticoid receptor interaction involving the amino-terminal domain of 
      HNF-6 and the DNA-binding domain of the receptor. Thus, in addition to its known 
      property of stimulating transcription of liver-expressed genes, HNF-6 can
      antagonize glucocorticoid-stimulated gene transcription.
FAU - Pierreux, C E
AU  - Pierreux CE
AD  - Hormone and Metabolic Research Unit, Universite catholique de Louvain and
      Christian de Duve Institute of Cellular Pathology, 75 Avenue Hippocrate, B-1200
      Brussels, Belgium.
FAU - Stafford, J
AU  - Stafford J
FAU - Demonte, D
AU  - Demonte D
FAU - Scott, D K
AU  - Scott DK
FAU - Vandenhaute, J
AU  - Vandenhaute J
FAU - O'Brien, R M
AU  - O'Brien RM
FAU - Granner, D K
AU  - Granner DK
FAU - Rousseau, G G
AU  - Rousseau GG
FAU - Lemaigre, F P
AU  - Lemaigre FP
LA  - eng
GR  - P60 DK020593/DK/NIDDK NIH HHS/United States
GR  - R01 DK035107/DK/NIDDK NIH HHS/United States
GR  - R37 DK035107/DK/NIDDK NIH HHS/United States
GR  - P30 DK020593/DK/NIDDK NIH HHS/United States
GR  - DK35107/DK/NIDDK NIH HHS/United States
GR  - DK20593/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Glucocorticoids)
RN  - 0 (Hepatocyte Nuclear Factor 6)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (ONECUT1 protein, human)
RN  - 0 (Onecut1 protein, rat)
RN  - 0 (Receptors, Glucocorticoid)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Trans-Activators)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - EC 1.13.12.- (Luciferases)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Dexamethasone/antagonists & inhibitors/*pharmacology
MH  - Genes, Reporter
MH  - Glucocorticoids/antagonists & inhibitors/*pharmacology
MH  - Hepatocyte Nuclear Factor 6
MH  - Homeodomain Proteins/genetics/*metabolism
MH  - Humans
MH  - Liver Neoplasms, Experimental
MH  - Luciferases/genetics
MH  - Promoter Regions, Genetic
MH  - Rats
MH  - Receptors, Glucocorticoid/genetics/*physiology
MH  - Recombinant Fusion Proteins/metabolism
MH  - TATA Box
MH  - Trans-Activators/genetics/*metabolism
MH  - Transfection
MH  - Tumor Cells, Cultured
PMC - PMC17715
EDAT- 1999/08/04 00:00
MHDA- 1999/08/04 00:01
CRDT- 1999/08/04 00:00
PHST- 1999/08/04 00:00 [pubmed]
PHST- 1999/08/04 00:01 [medline]
PHST- 1999/08/04 00:00 [entrez]
AID - 10.1073/pnas.96.16.8961 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):8961-6. doi: 10.1073/pnas.96.16.8961.