CRISPR reveals a distal super-enhancer required for Sox2 expression in mouse embryonic stem cells.
The pluripotency of embryonic stem cells (ESCs) is maintained by a small group of master transcription factors including Oct4, Sox2 and Nanog. These core factors form a regulatory circuit controlling the transcription of a number of pluripotency factors including themselves. Although previous studie...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4259346?pdf=render |
| _version_ | 1819163083221762048 |
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| author | Yan Li Chloe M Rivera Haruhiko Ishii Fulai Jin Siddarth Selvaraj Ah Young Lee Jesse R Dixon Bing Ren |
| author_facet | Yan Li Chloe M Rivera Haruhiko Ishii Fulai Jin Siddarth Selvaraj Ah Young Lee Jesse R Dixon Bing Ren |
| author_sort | Yan Li |
| collection | DOAJ |
| description | The pluripotency of embryonic stem cells (ESCs) is maintained by a small group of master transcription factors including Oct4, Sox2 and Nanog. These core factors form a regulatory circuit controlling the transcription of a number of pluripotency factors including themselves. Although previous studies have identified transcriptional regulators of this core network, the cis-regulatory DNA sequences required for the transcription of these key pluripotency factors remain to be defined. We analyzed epigenomic data within the 1.5 Mb gene-desert regions around the Sox2 gene and identified a 13kb-long super-enhancer (SE) located 100kb downstream of Sox2 in mouse ESCs. This SE is occupied by Oct4, Sox2, Nanog, and the mediator complex, and physically interacts with the Sox2 locus via DNA looping. Using a simple and highly efficient double-CRISPR genome editing strategy we deleted the entire 13-kb SE and characterized transcriptional defects in the resulting monoallelic and biallelic deletion clones with RNA-seq. We showed that the SE is responsible for over 90% of Sox2 expression, and Sox2 is the only target gene along the chromosome. Our results support the functional significance of a SE in maintaining the pluripotency transcription program in mouse ESCs. |
| first_indexed | 2024-12-22T17:38:29Z |
| format | Article |
| id | doaj.art-0e24ffcf8509483e901078173ca87330 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T17:38:29Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-0e24ffcf8509483e901078173ca873302022-12-21T18:18:28ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01912e11448510.1371/journal.pone.0114485CRISPR reveals a distal super-enhancer required for Sox2 expression in mouse embryonic stem cells.Yan LiChloe M RiveraHaruhiko IshiiFulai JinSiddarth SelvarajAh Young LeeJesse R DixonBing RenThe pluripotency of embryonic stem cells (ESCs) is maintained by a small group of master transcription factors including Oct4, Sox2 and Nanog. These core factors form a regulatory circuit controlling the transcription of a number of pluripotency factors including themselves. Although previous studies have identified transcriptional regulators of this core network, the cis-regulatory DNA sequences required for the transcription of these key pluripotency factors remain to be defined. We analyzed epigenomic data within the 1.5 Mb gene-desert regions around the Sox2 gene and identified a 13kb-long super-enhancer (SE) located 100kb downstream of Sox2 in mouse ESCs. This SE is occupied by Oct4, Sox2, Nanog, and the mediator complex, and physically interacts with the Sox2 locus via DNA looping. Using a simple and highly efficient double-CRISPR genome editing strategy we deleted the entire 13-kb SE and characterized transcriptional defects in the resulting monoallelic and biallelic deletion clones with RNA-seq. We showed that the SE is responsible for over 90% of Sox2 expression, and Sox2 is the only target gene along the chromosome. Our results support the functional significance of a SE in maintaining the pluripotency transcription program in mouse ESCs.http://europepmc.org/articles/PMC4259346?pdf=render |
| spellingShingle | Yan Li Chloe M Rivera Haruhiko Ishii Fulai Jin Siddarth Selvaraj Ah Young Lee Jesse R Dixon Bing Ren CRISPR reveals a distal super-enhancer required for Sox2 expression in mouse embryonic stem cells. PLoS ONE |
| title | CRISPR reveals a distal super-enhancer required for Sox2 expression in mouse embryonic stem cells. |
| title_full | CRISPR reveals a distal super-enhancer required for Sox2 expression in mouse embryonic stem cells. |
| title_fullStr | CRISPR reveals a distal super-enhancer required for Sox2 expression in mouse embryonic stem cells. |
| title_full_unstemmed | CRISPR reveals a distal super-enhancer required for Sox2 expression in mouse embryonic stem cells. |
| title_short | CRISPR reveals a distal super-enhancer required for Sox2 expression in mouse embryonic stem cells. |
| title_sort | crispr reveals a distal super enhancer required for sox2 expression in mouse embryonic stem cells |
| url | http://europepmc.org/articles/PMC4259346?pdf=render |
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