PMID- 21527498
OWN - NLM
STAT- MEDLINE
DCOM- 20110920
LR  - 20211020
IS  - 1944-9917 (Electronic)
IS  - 0888-8809 (Print)
IS  - 0888-8809 (Linking)
VI  - 25
IP  - 6
DP  - 2011 Jun
TI  - Expanding the paradigm for estrogen receptor binding and transcriptional 
      activation.
PG  - 980-94
LID - 10.1210/me.2010-0302 [doi]
AB  - Estrogen receptor (ER) binds to a spectrum of functional estrogen response 
      elements (ERE) within the human genome, including ERE half-sites (HERE), inverted 
      and direct repeats. This has been confounding, because ER has been reported to 
      bind weakly, if at all, to these sites in vitro. We show that ER binds strongly 
      to these nonconventional EREs, and the binding is enhanced by the presence of 
      high-mobility group protein B1 (HMGB1). Collectively, these and previous findings 
      reinforce the notion of the plasticity of strong ER/ERE interactions, consistent 
      with their broader range of observed binding specificity. In addition, transient 
      transfection studies using luciferase reporter gene assays show that these EREs 
      drive luciferase activity, and HMGB1 enhances transcriptional activity. 
      Furthermore, HMGB1 gene expression knockdown results in a precipitous drop in 
      luciferase activity, suggesting a prominent role for HMGB1 in activation of 
      estrogen/ER-responsive genes. Therefore, these data advocate that the minimal 
      target site for ER is a cHERE (consensus HERE) that occurs in many different 
      contexts and that HMGB1 enhances both the binding affinity and transcriptional 
      activity. This challenges the current paradigm for ER binding affinity and 
      functional activity and suggests that the paradigm requires significant 
      reevaluation and modification. These findings also suggest a possible mechanism 
      for a cross talk between genes regulated by ER and class II nuclear receptors.
FAU - Joshi, S R
AU  - Joshi SR
AD  - Department of Chemistry, Bowling Green State University, Bowling Green, Ohio 
      43403, USA.
FAU - Ghattamaneni, R B
AU  - Ghattamaneni RB
FAU - Scovell, W M
AU  - Scovell WM
LA  - eng
GR  - R15 GM054357/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20110428
PL  - United States
TA  - Mol Endocrinol
JT  - Molecular endocrinology (Baltimore, Md.)
JID - 8801431
RN  - 0 (Estrogens)
RN  - 0 (HMGB1 Protein)
RN  - 0 (Receptors, Estrogen)
RN  - EC 1.13.12.5 (Luciferases, Renilla)
SB  - IM
MH  - Base Sequence/genetics
MH  - Cell Line, Tumor
MH  - Electrophoretic Mobility Shift Assay
MH  - Estrogens/pharmacology
MH  - Genes, Reporter
MH  - HMGB1 Protein/chemistry/*genetics/metabolism
MH  - Humans
MH  - Luciferases, Renilla/biosynthesis/genetics
MH  - Models, Genetic
MH  - Molecular Sequence Data
MH  - Neoplasms/genetics/metabolism
MH  - RNA Interference
MH  - Receptors, Estrogen/chemistry/genetics/*metabolism
MH  - Response Elements
MH  - Tandem Repeat Sequences/genetics
MH  - Transcription, Genetic/drug effects
MH  - *Transcriptional Activation/drug effects
PMC - PMC3100604
EDAT- 2011/04/30 06:00
MHDA- 2011/09/21 06:00
PMCR- 2012/06/01
CRDT- 2011/04/30 06:00
PHST- 2011/04/30 06:00 [entrez]
PHST- 2011/04/30 06:00 [pubmed]
PHST- 2011/09/21 06:00 [medline]
PHST- 2012/06/01 00:00 [pmc-release]
AID - me.2010-0302 [pii]
AID - me-10-0302 [pii]
AID - 10.1210/me.2010-0302 [doi]
PST - ppublish
SO  - Mol Endocrinol. 2011 Jun;25(6):980-94. doi: 10.1210/me.2010-0302. Epub 2011 Apr 
      28.