PMID- 11069927
OWN - NLM
STAT- MEDLINE
DCOM- 20010621
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 276
IP  - 6
DP  - 2001 Feb 9
TI  - Role of accessory factors and steroid receptor coactivator 1 in the regulation of 
      phosphoenolpyruvate carboxykinase gene transcription by glucocorticoids.
PG  - 3811-9
AB  - In the liver, glucocorticoids induce a 10-15-fold increase in the rate of 
      transcription of the phosphoenolpyruvate carboxykinase (PEPCK) gene, which 
      encodes a key gluconeogenic enzyme. This induction requires a multicomponent 
      glucocorticoid response unit (GRU) comprised of four glucocorticoid accessory 
      factor (AF) elements and two glucocorticoid receptor binding sites. We show that 
      the AFs that bind the gAF1, gAF2, and gAF3 elements (hepatocyte nuclear factor 
      [HNF]4/chicken ovalbumin upstream promoter transcription factor 1 and HNF3beta) 
      all interact with steroid receptor coactivator 1 (SRC1). This suggests that the 
      AFs function in part by recruiting coactivators to the GRU. The binding of a 
      GAL4-SRC1 chimeric protein completely restores the glucocorticoid induction that 
      is lost when any one of these elements is replaced with a GAL4 binding site. 
      Thus, when SRC1 is recruited directly to gAF1, gAF2, or gAF3, the requirement for 
      the corresponding AF is bypassed. Surprisingly, glucocorticoid receptor is still 
      required when SRC1 is recruited directly to the GAL4 site, suggesting a role for 
      the receptor in activating SRC1 in the context of the GRU. Structural variants of 
      GAL4-SRC1 were used to identify requirements for the basic-helix-loop-helix and 
      histone acetyltransferase domains of SRC1, and these are specific to the region 
      of the promoter to which the coactivator is recruited.
FAU - Stafford, J M
AU  - Stafford JM
AD  - Department of Molecular Physiology and Biophysics, Vanderbilt University School 
      of Medicine and the Nashville Veterans Administration Hospital, Nashville, 
      Tennessee 37232, USA.
FAU - Waltner-Law, M
AU  - Waltner-Law M
FAU - Granner, D K
AU  - Granner DK
LA  - eng
GR  - DK20593/DK/NIDDK NIH HHS/United States
GR  - DK35107/DK/NIDDK NIH HHS/United States
GR  - GM07347/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20001107
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DNA Primers)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Fungal Proteins)
RN  - 0 (GAL4 protein, S cerevisiae)
RN  - 0 (Glucocorticoids)
RN  - 0 (Receptors, Interferon)
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - 0 (Transcription Factors)
RN  - EC 2.3.1.48 (Histone Acetyltransferases)
RN  - EC 2.3.1.48 (Nuclear Receptor Coactivator 1)
RN  - EC 4.1.1.49 (Phosphoenolpyruvate Carboxykinase (ATP))
SB  - IM
MH  - Base Sequence
MH  - Cell Line
MH  - DNA Primers
MH  - DNA-Binding Proteins
MH  - Fungal Proteins/metabolism
MH  - Gene Expression Regulation, Enzymologic/*physiology
MH  - Glucocorticoids/*pharmacology
MH  - Histone Acetyltransferases
MH  - Nuclear Receptor Coactivator 1
MH  - Phosphoenolpyruvate Carboxykinase (ATP)/*genetics
MH  - Receptors, Interferon/*physiology
MH  - *Saccharomyces cerevisiae Proteins
MH  - Transcription Factors/metabolism/*physiology
MH  - Transcription, Genetic/*physiology
EDAT- 2000/11/09 00:00
MHDA- 2001/06/22 10:01
CRDT- 2000/11/09 00:00
PHST- 2000/11/09 00:00 [pubmed]
PHST- 2001/06/22 10:01 [medline]
PHST- 2000/11/09 00:00 [entrez]
AID - S0021-9258(18)46373-9 [pii]
AID - 10.1074/jbc.M009389200 [doi]
PST - ppublish
SO  - J Biol Chem. 2001 Feb 9;276(6):3811-9. doi: 10.1074/jbc.M009389200. Epub 2000 Nov 
      7.