UM  > 健康科學學院
Integrative model of genomic factors for determining binding site selection by estrogen receptor-α
Joseph R.; Orlov Y.L.; Huss M.; Sun W.; Li Kong S.; Ukil L.; Pan Y.F.; Li G.; Lim M.; Thomsen J.S.; Ruan Y.; Clarke N.D.; Prabhakar S.; Cheung E.; Liu E.T.
2010-12-01
Source PublicationMolecular Systems Biology
ISSN17444292 17444292
Volume6
Abstract

A major question in transcription factor (TF) biology is why a TF binds to only a small fraction of motif eligible binding sites in the genome. Using the estrogen receptor-α as a model system, we sought to explicitly define parameters that determine TF-binding site selection. By examining 12 genetic and epigenetic parameters, we find that an energetically favorable estrogen response element (ERE) motif sequence, co-occupancy by the TF FOXA1, the presence of the H3K4me1 mark and an open chromatin configuration in the pre-ligand state provide specificity for ER binding. These factors can model estrogen-induced ER binding with high accuracy (ROC-AUC=0.95 and 0.88 using different genomic backgrounds). Moreover, when assessed in another estrogen-responsive cell line, this model was highly predictive for ERα binding (ROC-AUC=0.86). Variance in binding site selection between MCF-7 and T47D resides in sites with suboptimal ERE motifs, but modulated by the chromatin configuration. These results suggest a definable interplay between sequence motifs and local chromatin in selecting TF binding. © 2010 EMBO and Macmillan Publishers Limited All rights reserved.

KeywordChromatin Dna Binding Modeling Recognition Motifs Transcription Factor
DOI10.1038/msb.2010.109
URLView the original
Indexed BySCI
WOS Research AreaBiochemistry & Molecular Biology
WOS SubjectBiochemistry & Molecular Biology
WOS IDWOS:000285930400009
Fulltext Access
Citation statistics
Cited Times [WOS]:109   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
AffiliationA-Star, Genome Institute of Singapore
Recommended Citation
GB/T 7714
Joseph R.,Orlov Y.L.,Huss M.,et al. Integrative model of genomic factors for determining binding site selection by estrogen receptor-α[J]. Molecular Systems Biology,2010,6.
APA Joseph R..,Orlov Y.L..,Huss M..,Sun W..,Li Kong S..,...&Liu E.T..(2010).Integrative model of genomic factors for determining binding site selection by estrogen receptor-α.Molecular Systems Biology,6.
MLA Joseph R.,et al."Integrative model of genomic factors for determining binding site selection by estrogen receptor-α".Molecular Systems Biology 6(2010).
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Joseph R.]'s Articles
[Orlov Y.L.]'s Articles
[Huss M.]'s Articles
Baidu academic
Similar articles in Baidu academic
[Joseph R.]'s Articles
[Orlov Y.L.]'s Articles
[Huss M.]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Joseph R.]'s Articles
[Orlov Y.L.]'s Articles
[Huss M.]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.