PMID- 23019147
OWN - NLM
STAT- MEDLINE
DCOM- 20130411
LR  - 20221111
IS  - 1549-5469 (Electronic)
IS  - 1088-9051 (Print)
IS  - 1088-9051 (Linking)
VI  - 22
IP  - 11
DP  - 2012 Nov
TI  - Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of 
      sites in a cell type-specific manner.
PG  - 2153-62
LID - 10.1101/gr.135681.111 [doi]
AB  - Endogenous estrogens that are synthesized in the body impact gene regulation by 
      activating estrogen receptors in diverse cell types. Exogenous compounds that 
      have estrogenic properties can also be found circulating in the blood in both 
      children and adults. The genome-wide impact of these environmental estrogens on 
      gene regulation is unclear. To obtain an integrated view of gene regulation in 
      response to environmental and endogenous estrogens on a genome-wide scale, we 
      performed ChIP-seq to identify estrogen receptor 1 (ESR1; previously estrogen 
      receptor alpha) binding sites, and RNA-seq in endometrial cancer cells exposed to 
      bisphenol A (BPA; found in plastics), genistein (GEN; found in soybean), or 
      17beta-estradiol (E2; an endogenous estrogen). GEN and BPA treatment induces 
      thousands of ESR1 binding sites and >50 gene expression changes, representing a 
      subset of E2-induced gene regulation changes. Genes affected by E2 were highly 
      enriched for ribosome-associated proteins; however, GEN and BPA failed to 
      regulate most ribosome-associated proteins and instead enriched for transporters 
      of carboxylic acids. Treatment-dependent changes in gene expression were 
      associated with treatment-dependent ESR1 binding sites, with the exception that 
      many genes up-regulated by E2 harbored a BPA-induced ESR1 binding site but failed 
      to show any expression change after BPA treatment. GEN and BPA exhibited a 
      similar relationship to E2 in the breast cancer line T-47D, where cell type 
      specificity played a much larger role than treatment specificity. Overall, both 
      environmental estrogens clearly regulate gene expression through ESR1 on a 
      genome-wide scale, although with lower potency resulting in less ESR1 binding 
      sites and less gene expression changes compared to the endogenous estrogen, E2.
FAU - Gertz, Jason
AU  - Gertz J
AD  - HudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, USA.
FAU - Reddy, Timothy E
AU  - Reddy TE
FAU - Varley, Katherine E
AU  - Varley KE
FAU - Garabedian, Michael J
AU  - Garabedian MJ
FAU - Myers, Richard M
AU  - Myers RM
LA  - eng
GR  - EP-C-12-028/EPA/EPA/United States
GR  - U54 HG004576/HG/NHGRI NIH HHS/United States
GR  - 5U54HG004576/HG/NHGRI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120926
PL  - United States
TA  - Genome Res
JT  - Genome research
JID - 9518021
RN  - 0 (Benzhydryl Compounds)
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (Estrogens, Non-Steroidal)
RN  - 0 (Phenols)
RN  - 0 (Phytoestrogens)
RN  - 4TI98Z838E (Estradiol)
RN  - DH2M523P0H (Genistein)
RN  - MLT3645I99 (bisphenol A)
SB  - IM
MH  - Benzhydryl Compounds/*pharmacology
MH  - Binding Sites
MH  - Cell Line, Tumor
MH  - Estradiol/metabolism
MH  - Estrogen Receptor alpha/*metabolism
MH  - Estrogens, Non-Steroidal/*pharmacology
MH  - Gene Expression Regulation, Neoplastic
MH  - Genetic Loci
MH  - Genistein/*pharmacology
MH  - Genome, Human
MH  - Humans
MH  - Organ Specificity
MH  - Phenols/*pharmacology
MH  - Phytoestrogens/*pharmacology
MH  - Sequence Analysis, RNA
MH  - Transcription, Genetic
MH  - Up-Regulation
PMC - PMC3483545
EDAT- 2012/09/29 06:00
MHDA- 2013/04/12 06:00
PMCR- 2013/05/01
CRDT- 2012/09/29 06:00
PHST- 2012/09/29 06:00 [entrez]
PHST- 2012/09/29 06:00 [pubmed]
PHST- 2013/04/12 06:00 [medline]
PHST- 2013/05/01 00:00 [pmc-release]
AID - gr.135681.111 [pii]
AID - 10.1101/gr.135681.111 [doi]
PST - ppublish
SO  - Genome Res. 2012 Nov;22(11):2153-62. doi: 10.1101/gr.135681.111. Epub 2012 Sep 
      26.