PMID- 23636943
OWN - NLM
STAT- MEDLINE
DCOM- 20140219
LR  - 20220321
IS  - 1549-5469 (Electronic)
IS  - 1088-9051 (Print)
IS  - 1088-9051 (Linking)
VI  - 23
IP  - 8
DP  - 2013 Aug
TI  - Enhancer transcripts mark active estrogen receptor binding sites.
PG  - 1210-23
LID - 10.1101/gr.152306.112 [doi]
AB  - We have integrated and analyzed a large number of data sets from a variety of 
      genomic assays using a novel computational pipeline to provide a global view of 
      estrogen receptor 1 (ESR1; a.k.a. ERalpha) enhancers in MCF-7 human breast cancer 
      cells. Using this approach, we have defined a class of primary transcripts 
      (eRNAs) that are transcribed uni- or bidirectionally from estrogen receptor 
      binding sites (ERBSs) with an average transcription unit length of  approximately 3-5 kb. The 
      majority are up-regulated by short treatments with estradiol (i.e., 10, 25, or 40 
      min) with kinetics that precede or match the induction of the target genes. The 
      production of eRNAs at ERBSs is strongly correlated with the enrichment of a 
      number of genomic features that are associated with enhancers (e.g., H3K4me1, 
      H3K27ac, EP300/CREBBP, RNA polymerase II, open chromatin architecture), as well 
      as enhancer looping to target gene promoters. In the absence of eRNA production, 
      strong enrichment of these features is not observed, even though ESR1 binding is 
      evident. We find that flavopiridol, a CDK9 inhibitor that blocks transcription 
      elongation, inhibits eRNA production but does not affect other molecular 
      indicators of enhancer activity, suggesting that eRNA production occurs after the 
      assembly of active enhancers. Finally, we show that an enhancer transcription 
      "signature" based on GRO-seq data can be used for de novo enhancer prediction 
      across cell types. Together, our studies shed new light on the activity of ESR1 
      at its enhancer sites and provide new insights about enhancer function.
FAU - Hah, Nasun
AU  - Hah N
AD  - Department of Molecular Biology and Genetics, Cornell University, Ithaca, New 
      York 14853, USA.
FAU - Murakami, Shino
AU  - Murakami S
FAU - Nagari, Anusha
AU  - Nagari A
FAU - Danko, Charles G
AU  - Danko CG
FAU - Kraus, W Lee
AU  - Kraus WL
LA  - eng
SI  - GEO/GSE43836
GR  - R01 DK058110/DK/NIDDK NIH HHS/United States
GR  - T32 HD052471/HD/NICHD NIH HHS/United States
GR  - DK058110/DK/NIDDK NIH HHS/United States
GR  - T32HD052471/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130501
PL  - United States
TA  - Genome Res
JT  - Genome research
JID - 9518021
RN  - 0 (ESR1 protein, human)
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (RNA, Untranslated)
RN  - 4TI98Z838E (Estradiol)
SB  - IM
MH  - Base Sequence
MH  - Binding Sites
MH  - Chromosome Mapping
MH  - Consensus Sequence
MH  - *Enhancer Elements, Genetic
MH  - Estradiol/physiology
MH  - Estrogen Receptor alpha/*physiology
MH  - *Gene Expression Regulation
MH  - Genome, Human
MH  - Humans
MH  - MCF-7 Cells
MH  - Molecular Sequence Annotation
MH  - RNA, Untranslated/*genetics
MH  - Transcription, Genetic
PMC - PMC3730096
EDAT- 2013/05/03 06:00
MHDA- 2014/02/20 06:00
PMCR- 2014/02/01
CRDT- 2013/05/03 06:00
PHST- 2013/05/03 06:00 [entrez]
PHST- 2013/05/03 06:00 [pubmed]
PHST- 2014/02/20 06:00 [medline]
PHST- 2014/02/01 00:00 [pmc-release]
AID - gr.152306.112 [pii]
AID - 10.1101/gr.152306.112 [doi]
PST - ppublish
SO  - Genome Res. 2013 Aug;23(8):1210-23. doi: 10.1101/gr.152306.112. Epub 2013 May 1.