Enhancer identification in mouse embryonic stem cells using integrative modeling of chromatin and genomic features
<p>Abstract</p> <p>Background</p> <p>Epigenetic modifications, transcription factor (TF) availability and differences in chromatin folding influence how the genome is interpreted by the transcriptional machinery responsible for gene expression. Enhancers buried in non-c...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2012-04-01
|
| Series: | BMC Genomics |
| Subjects: | |
| Online Access: | http://www.biomedcentral.com/1471-2164/13/152 |
| _version_ | 1818114573003128832 |
|---|---|
| author | Chen Chih-yu Morris Quaid Mitchell Jennifer A |
| author_facet | Chen Chih-yu Morris Quaid Mitchell Jennifer A |
| author_sort | Chen Chih-yu |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Epigenetic modifications, transcription factor (TF) availability and differences in chromatin folding influence how the genome is interpreted by the transcriptional machinery responsible for gene expression. Enhancers buried in non-coding regions are found to be associated with significant differences in histone marks between different cell types. In contrast, gene promoters show more uniform modifications across cell types. Here we used histone modification and chromatin-associated protein ChIP-Seq data sets in mouse embryonic stem (ES) cells as well as genomic features to identify functional enhancer regions. Using co-bound sites of OCT4, SOX2 and NANOG (co-OSN, validated enhancers) and co-bound sites of MYC and MYCN (limited enhancer activity) as enhancer positive and negative training sets, we performed multinomial logistic regression with LASSO regularization to identify key features.</p> <p>Results</p> <p>Cross validations reveal that a combination of p300, H3K4me1, MED12 and NIPBL features to be top signatures of co-OSN regions. Using a model from 10 signatures, 83% of top 1277 putative 1 kb enhancer regions (probability greater than or equal to 0.8) overlapped with at least one TF peak from 7 mouse ES cell ChIP-Seq data sets. These putative enhancers are associated with increased gene expression of neighbouring genes and significantly enriched in multiple TF bound loci in agreement with combinatorial models of TF binding. Furthermore, we identified several motifs of known TFs significantly enriched in putative enhancer regions compared to random promoter regions and background. Comparison with an active H3K27ac mark in various cell types confirmed cell type-specificity of these enhancers.</p> <p>Conclusions</p> <p>The top enhancer signatures we identified (p300, H3K4me1, MED12 and NIPBL) will allow for the identification of cell type-specific enhancer regions in diverse cell types.</p> |
| first_indexed | 2024-12-11T03:52:52Z |
| format | Article |
| id | doaj.art-2c641fe301934b87aa38bf6ba3f9417c |
| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-12-11T03:52:52Z |
| publishDate | 2012-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genomics |
| spelling | doaj.art-2c641fe301934b87aa38bf6ba3f9417c2022-12-22T01:21:51ZengBMCBMC Genomics1471-21642012-04-0113115210.1186/1471-2164-13-152Enhancer identification in mouse embryonic stem cells using integrative modeling of chromatin and genomic featuresChen Chih-yuMorris QuaidMitchell Jennifer A<p>Abstract</p> <p>Background</p> <p>Epigenetic modifications, transcription factor (TF) availability and differences in chromatin folding influence how the genome is interpreted by the transcriptional machinery responsible for gene expression. Enhancers buried in non-coding regions are found to be associated with significant differences in histone marks between different cell types. In contrast, gene promoters show more uniform modifications across cell types. Here we used histone modification and chromatin-associated protein ChIP-Seq data sets in mouse embryonic stem (ES) cells as well as genomic features to identify functional enhancer regions. Using co-bound sites of OCT4, SOX2 and NANOG (co-OSN, validated enhancers) and co-bound sites of MYC and MYCN (limited enhancer activity) as enhancer positive and negative training sets, we performed multinomial logistic regression with LASSO regularization to identify key features.</p> <p>Results</p> <p>Cross validations reveal that a combination of p300, H3K4me1, MED12 and NIPBL features to be top signatures of co-OSN regions. Using a model from 10 signatures, 83% of top 1277 putative 1 kb enhancer regions (probability greater than or equal to 0.8) overlapped with at least one TF peak from 7 mouse ES cell ChIP-Seq data sets. These putative enhancers are associated with increased gene expression of neighbouring genes and significantly enriched in multiple TF bound loci in agreement with combinatorial models of TF binding. Furthermore, we identified several motifs of known TFs significantly enriched in putative enhancer regions compared to random promoter regions and background. Comparison with an active H3K27ac mark in various cell types confirmed cell type-specificity of these enhancers.</p> <p>Conclusions</p> <p>The top enhancer signatures we identified (p300, H3K4me1, MED12 and NIPBL) will allow for the identification of cell type-specific enhancer regions in diverse cell types.</p>http://www.biomedcentral.com/1471-2164/13/152EnhancerEmbryonic stem cellsTranscription factorChIP-SeqHistone methylationRegulation of gene expression |
| spellingShingle | Chen Chih-yu Morris Quaid Mitchell Jennifer A Enhancer identification in mouse embryonic stem cells using integrative modeling of chromatin and genomic features BMC Genomics Enhancer Embryonic stem cells Transcription factor ChIP-Seq Histone methylation Regulation of gene expression |
| title | Enhancer identification in mouse embryonic stem cells using integrative modeling of chromatin and genomic features |
| title_full | Enhancer identification in mouse embryonic stem cells using integrative modeling of chromatin and genomic features |
| title_fullStr | Enhancer identification in mouse embryonic stem cells using integrative modeling of chromatin and genomic features |
| title_full_unstemmed | Enhancer identification in mouse embryonic stem cells using integrative modeling of chromatin and genomic features |
| title_short | Enhancer identification in mouse embryonic stem cells using integrative modeling of chromatin and genomic features |
| title_sort | enhancer identification in mouse embryonic stem cells using integrative modeling of chromatin and genomic features |
| topic | Enhancer Embryonic stem cells Transcription factor ChIP-Seq Histone methylation Regulation of gene expression |
| url | http://www.biomedcentral.com/1471-2164/13/152 |
| work_keys_str_mv | AT chenchihyu enhanceridentificationinmouseembryonicstemcellsusingintegrativemodelingofchromatinandgenomicfeatures AT morrisquaid enhanceridentificationinmouseembryonicstemcellsusingintegrativemodelingofchromatinandgenomicfeatures AT mitchelljennifera enhanceridentificationinmouseembryonicstemcellsusingintegrativemodelingofchromatinandgenomicfeatures |