Integrative model of genomic factors for determining binding site selection by estrogen receptor‐α
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...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2010-01-01
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| Series: | Molecular Systems Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/msb.2010.109 |
| _version_ | 1797280251074576384 |
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| author | Roy Joseph Yuriy L Orlov Mikael Huss Wenjie Sun Say Li Kong Leena Ukil You Fu Pan Guoliang Li Michael Lim Jane S Thomsen Yijun Ruan Neil D Clarke Shyam Prabhakar Edwin Cheung Edison T Liu |
| author_facet | Roy Joseph Yuriy L Orlov Mikael Huss Wenjie Sun Say Li Kong Leena Ukil You Fu Pan Guoliang Li Michael Lim Jane S Thomsen Yijun Ruan Neil D Clarke Shyam Prabhakar Edwin Cheung Edison T Liu |
| author_sort | Roy Joseph |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T16:38:24Z |
| format | Article |
| id | doaj.art-7bdfe7fe36ae4c3688f07e0338e42aab |
| institution | Directory Open Access Journal |
| issn | 1744-4292 |
| language | English |
| last_indexed | 2024-03-07T16:38:24Z |
| publishDate | 2010-01-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj.art-7bdfe7fe36ae4c3688f07e0338e42aab2024-03-03T09:22:55ZengSpringer NatureMolecular Systems Biology1744-42922010-01-0161n/an/a10.1038/msb.2010.109Integrative model of genomic factors for determining binding site selection by estrogen receptor‐αRoy Joseph0Yuriy L Orlov1Mikael Huss2Wenjie Sun3Say Li Kong4Leena Ukil5You Fu Pan6Guoliang Li7Michael Lim8Jane S Thomsen9Yijun Ruan10Neil D Clarke11Shyam Prabhakar12Edwin Cheung13Edison T Liu14Genome Institute of Singapore, Agency for Science, Technology and Research SingaporeGenome Institute of Singapore, Agency for Science, Technology and Research SingaporeGenome Institute of Singapore, Agency for Science, Technology and Research SingaporeGenome Institute of Singapore, Agency for Science, Technology and Research SingaporeGenome Institute of Singapore, Agency for Science, Technology and Research SingaporeGenome Institute of Singapore, Agency for Science, Technology and Research SingaporeGenome Institute of Singapore, Agency for Science, Technology and Research SingaporeGenome Institute of Singapore, Agency for Science, Technology and Research SingaporeGenome Institute of Singapore, Agency for Science, Technology and Research SingaporeGenome Institute of Singapore, Agency for Science, Technology and Research SingaporeGenome Institute of Singapore, Agency for Science, Technology and Research SingaporeGenome Institute of Singapore, Agency for Science, Technology and Research SingaporeGenome Institute of Singapore, Agency for Science, Technology and Research SingaporeGenome Institute of Singapore, Agency for Science, Technology and Research SingaporeGenome Institute of Singapore, Agency for Science, Technology and Research SingaporeA 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.https://doi.org/10.1038/msb.2010.109chromatinDNA bindingmodelingrecognition motifstranscription factor |
| spellingShingle | Roy Joseph Yuriy L Orlov Mikael Huss Wenjie Sun Say Li Kong Leena Ukil You Fu Pan Guoliang Li Michael Lim Jane S Thomsen Yijun Ruan Neil D Clarke Shyam Prabhakar Edwin Cheung Edison T Liu Integrative model of genomic factors for determining binding site selection by estrogen receptor‐α Molecular Systems Biology chromatin DNA binding modeling recognition motifs transcription factor |
| title | Integrative model of genomic factors for determining binding site selection by estrogen receptor‐α |
| title_full | Integrative model of genomic factors for determining binding site selection by estrogen receptor‐α |
| title_fullStr | Integrative model of genomic factors for determining binding site selection by estrogen receptor‐α |
| title_full_unstemmed | Integrative model of genomic factors for determining binding site selection by estrogen receptor‐α |
| title_short | Integrative model of genomic factors for determining binding site selection by estrogen receptor‐α |
| title_sort | integrative model of genomic factors for determining binding site selection by estrogen receptor α |
| topic | chromatin DNA binding modeling recognition motifs transcription factor |
| url | https://doi.org/10.1038/msb.2010.109 |
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