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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Apr 27, 2015 |
| Title |
Epigenetic and genetic features that lead to discovery of enhancer function |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
The ability to measure epigenetic features, such as histone modifications and occupancy by transcription factors and co-activators, on a genome-wide scale is advancing the accuracy of CRM predictions. While integration of signals from multiple features is expected to improve predictions, the contribution of each feature to prediction accuracy is not known. We began with predictions of 4,915 erythroid enhancers based on genomic occupancy by TAL1, a key hematopoietic transcription factor that is strongly associated with gene induction in erythroid cells. Seventy of these DNA segments occupied by TAL1 (TAL1 OSs) were tested by transient transfections of cultured hematopoietic cells, and 56% of these were active as enhancers. Sixty-six TAL1 OSs were evaluated in transgenic mouse embryos, and 65% of these were active enhancers in various tissues. Inclusion of additional epigenetic features improved the prediction accuracy, with combinations of TAL1, GATA1, EP300, H3K4me1, and H3K27ac giving high accuracy of enhancer prediction (70%-75% success depending on method of clustering) while maintaining good sensitivity and specificity. Motifs that distinguish active from inactive TAL1 OSs implicate IRFs, STATs, and FOX protein families as candidate positive co-factors with TAL1, while REST (NRSF) and HOX family proteins are implicated in inactivity. While signals for evolutionary constraint were weak over the entire TAL1-bound DNA segments regardless of activity in either assay, phylogenetic preservation of a TF-binding site motif was associated with enhancer activity.
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| Overall design |
The contribution of 8 epigenetic features including H3K27ac to identification of enhancers in 24h-induced G1E-ER4 cells.
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| Contributor(s) |
Dogan N, Wu W, Morrissy CS, Chen K, Stronestrom A, Long M, Keller CA, Cheng Y, Jain D, Visel A, Pennacchio LA, Weiss MJ, Blobel GA, Hardison RC |
| Citation(s) |
25984238 |
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| Submission date |
Sep 11, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Ross Hardison |
| E-mail(s) |
rch8@psu.edu
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| Organization name |
Pennsylvania State University
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| Street address |
303 Wartik Lab
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| City |
University Park |
| State/province |
PA |
| ZIP/Postal code |
16802 |
| Country |
USA |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (4)
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| Relations |
| Reanalysis of |
GSM923567 |
| Reanalysis of |
GSM923572 |
| Reanalysis of |
GSM923576 |
| Reanalysis of |
GSM946519 |
| Reanalysis of |
GSM946520 |
| Reanalysis of |
GSM946534 |
| Reanalysis of |
GSM946537 |
| Reanalysis of |
GSM946545 |
| Reanalysis of |
GSM995449 |
| Reanalysis of |
GSM912921 |
| Reanalysis of |
GSM912893 |
| BioProject |
PRJNA262049 |
| SRA |
SRP047493 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE61349_DoganSupplementalTables-1.xlsx |
1.1 Mb |
(ftp)(http) |
XLSX |
| GSE61349_RAW.tar |
14.0 Gb |
(http)(custom) |
TAR (of BIGWIG, BROADPEAK) |
| GSE61349_er4Pool.bigWig |
5.1 Gb |
(ftp)(http) |
BIGWIG |
| GSE61349_er4Pool.broadpeak.gz |
718.0 Kb |
(ftp)(http) |
BROADPEAK |
| GSE61349_g1ePool.bigWig |
3.9 Gb |
(ftp)(http) |
BIGWIG |
| GSE61349_g1ePool.broadpeak.gz |
611.4 Kb |
(ftp)(http) |
BROADPEAK |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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