PMID- 18801933
OWN - NLM
STAT- MEDLINE
DCOM- 20090306
LR  - 20201209
IS  - 0888-8809 (Print)
IS  - 1944-9917 (Electronic)
IS  - 0888-8809 (Linking)
VI  - 22
IP  - 12
DP  - 2008 Dec
TI  - Tissue- and context-dependent modulation of hormonal sensitivity of 
      glucocorticoid-responsive genes by hexamethylene bisacetamide-inducible protein 
      1.
PG  - 2609-23
LID - 10.1210/me.2008-0101 [doi]
AB  - Physiological and pharmacological processes mediated by glucocorticoids involve 
      tissue- and context-specific regulation of glucocorticoid-responsive gene 
      expression via glucocorticoid receptor (GR). However, the molecular mechanisms 
      underlying such highly coordinated regulation of glucocorticoid actions remain to 
      be studied. We here addressed this issue using atp1a1 and scnn1a, both of which 
      are up-regulated in response to corticosteroids in human embryonic kidney-derived 
      293 cells, but resistant in liver-derived HepG2 cells. Hexamethylene 
      bisacetamide-inducible protein 1 (HEXIM1) represses gene expression via, at 
      least, two distinct mechanisms, i.e. positive transcription elongation factor b 
      sequestration and direct interaction with GR, and is relatively high in HepG2 
      cells compared with 293 cells. Given this, we focused on the role of HEXIM1 in 
      transcriptional regulation of these GR target genes. In HepG2 cells, hormone 
      resistance of atp1a1 and scnn1a was diminished by either knockdown of HEXIM1 or 
      overexpression of GR. Such a positive effect of exogenous expression of GR was 
      counteracted by concomitant overexpression of HEXIM1, indicating the balance 
      between GR and HEXIM1 modulates hormonal sensitivity of these genes. In support 
      of this, the hormone-dependent recruitment of RNA polymerase II onto atp1a1 
      promoter was in parallel with that of GR. Moreover, we revealed that not positive 
      transcription elongation factor b-suppressing activity but direct interaction 
      with GR of HEXIM1 plays a major role in suppression of promoter recruitment of 
      the receptor and subsequent atp1a1 and scnn1a gene activation. Collectively, we 
      may conclude that HEXIM1 may participate in tissue-selective determination of 
      glucocorticoid sensitivity via direct interaction with GR at least in certain 
      gene sets including atp1a1 and scnn1a.
FAU - Shimizu, Noriaki
AU  - Shimizu N
AD  - Division of Clinical Immunology, Advanced Clinical Research Center, Research 
      Hospital, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
FAU - Yoshikawa, Noritada
AU  - Yoshikawa N
FAU - Wada, Tadashi
AU  - Wada T
FAU - Handa, Hiroshi
AU  - Handa H
FAU - Sano, Motoaki
AU  - Sano M
FAU - Fukuda, Keiichi
AU  - Fukuda K
FAU - Suematsu, Makoto
AU  - Suematsu M
FAU - Sawai, Takashi
AU  - Sawai T
FAU - Morimoto, Chikao
AU  - Morimoto C
FAU - Tanaka, Hirotoshi
AU  - Tanaka H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080918
PL  - United States
TA  - Mol Endocrinol
JT  - Molecular endocrinology (Baltimore, Md.)
JID - 8801431
RN  - 0 (Epithelial Sodium Channels)
RN  - 0 (Glucocorticoids)
RN  - 0 (HEXIM1 protein, human)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (Receptors, Glucocorticoid)
RN  - 0 (SCNN1A protein, human)
RN  - 0 (Transcription Factors)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - EC 3.6.1.- (ATP1A1 protein, human)
RN  - EC 7.2.2.13 (Sodium-Potassium-Exchanging ATPase)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - COS Cells
MH  - Cells, Cultured
MH  - Chlorocebus aethiops
MH  - Dexamethasone/pharmacology
MH  - Drug Resistance/*genetics
MH  - Epithelial Sodium Channels/genetics
MH  - Gene Expression Regulation/*drug effects
MH  - Glucocorticoids/*pharmacology
MH  - HeLa Cells
MH  - Humans
MH  - Molecular Sequence Data
MH  - Organ Specificity/drug effects/genetics
MH  - Protein Binding/drug effects
MH  - RNA-Binding Proteins/genetics/*physiology
MH  - Receptors, Glucocorticoid/metabolism/physiology
MH  - Sodium-Potassium-Exchanging ATPase/genetics
MH  - Tissue Distribution/drug effects
MH  - Transcription Factors
PMC - PMC5419410
EDAT- 2008/09/20 09:00
MHDA- 2009/03/07 09:00
PMCR- 2009/12/01
CRDT- 2008/09/20 09:00
PHST- 2008/09/20 09:00 [pubmed]
PHST- 2009/03/07 09:00 [medline]
PHST- 2008/09/20 09:00 [entrez]
PHST- 2009/12/01 00:00 [pmc-release]
AID - me.2008-0101 [pii]
AID - 10.1210/me.2008-0101 [doi]
PST - ppublish
SO  - Mol Endocrinol. 2008 Dec;22(12):2609-23. doi: 10.1210/me.2008-0101. Epub 2008 Sep 
      18.