Enforcement of developmental lineage specificity by transcription factor Oct1
Embryonic stem cells co-express Oct4 and Oct1, a related protein with similar DNA-binding specificity. To study the role of Oct1 in ESC pluripotency and transcriptional control, we constructed germline and inducible-conditional Oct1-deficient ESC lines. ESCs lacking Oct1 show normal appearance, self...
| Main Authors: | , , , , , , |
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| Format: | Article |
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eLife Sciences Publications, Ltd
2017
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| Online Access: | http://hdl.handle.net/1721.1/111796 https://orcid.org/0000-0001-8567-2049 |
| _version_ | 1826217199709192192 |
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| author | Shen, Zuolian Kang, Jinsuk Shakya, Arvind Tabaka, Marcin Jarboe, Elke A Regev, Aviv Tantin, Dean |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Shen, Zuolian Kang, Jinsuk Shakya, Arvind Tabaka, Marcin Jarboe, Elke A Regev, Aviv Tantin, Dean |
| author_sort | Shen, Zuolian |
| collection | MIT |
| description | Embryonic stem cells co-express Oct4 and Oct1, a related protein with similar DNA-binding specificity. To study the role of Oct1 in ESC pluripotency and transcriptional control, we constructed germline and inducible-conditional Oct1-deficient ESC lines. ESCs lacking Oct1 show normal appearance, self-renewal and growth but manifest defects upon differentiation. They fail to form beating cardiomyocytes, generate neurons poorly, form small, poorly differentiated teratomas, and cannot generate chimeric mice. Upon RA-mediated differentiation, Oct1-deficient cells induce lineage-appropriate developmentally poised genes poorly while lineage-inappropriate genes, including extra-embryonic genes, are aberrantly expressed. In ESCs, Oct1 co-occupies a specific set of targets with Oct4, but does not occupy differentially expressed developmental targets. Instead, Oct1 occupies these targets as cells differentiate and Oct4 declines. These results identify a dynamic interplay between Oct1 and Oct4, in particular during the critical window immediately after loss of pluripotency when cells make the earliest developmental fate decisions. |
| first_indexed | 2024-09-23T16:59:36Z |
| format | Article |
| id | mit-1721.1/111796 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T16:59:36Z |
| publishDate | 2017 |
| publisher | eLife Sciences Publications, Ltd |
| record_format | dspace |
| spelling | mit-1721.1/1117962022-10-03T09:41:04Z Enforcement of developmental lineage specificity by transcription factor Oct1 Shen, Zuolian Kang, Jinsuk Shakya, Arvind Tabaka, Marcin Jarboe, Elke A Regev, Aviv Tantin, Dean Massachusetts Institute of Technology. Department of Biology Regev, Aviv Embryonic stem cells co-express Oct4 and Oct1, a related protein with similar DNA-binding specificity. To study the role of Oct1 in ESC pluripotency and transcriptional control, we constructed germline and inducible-conditional Oct1-deficient ESC lines. ESCs lacking Oct1 show normal appearance, self-renewal and growth but manifest defects upon differentiation. They fail to form beating cardiomyocytes, generate neurons poorly, form small, poorly differentiated teratomas, and cannot generate chimeric mice. Upon RA-mediated differentiation, Oct1-deficient cells induce lineage-appropriate developmentally poised genes poorly while lineage-inappropriate genes, including extra-embryonic genes, are aberrantly expressed. In ESCs, Oct1 co-occupies a specific set of targets with Oct4, but does not occupy differentially expressed developmental targets. Instead, Oct1 occupies these targets as cells differentiate and Oct4 declines. These results identify a dynamic interplay between Oct1 and Oct4, in particular during the critical window immediately after loss of pluripotency when cells make the earliest developmental fate decisions. 2017-10-05T18:21:10Z 2017-10-05T18:21:10Z 2017-05 2016-08 2017-08-21T13:26:14Z Article http://purl.org/eprint/type/JournalArticle 2050-084X http://hdl.handle.net/1721.1/111796 Shen, Zuolian et al. “Enforcement of Developmental Lineage Specificity by Transcription Factor Oct1.” eLife 6 (May 2017): e20937 © 2017 Shen et al. https://orcid.org/0000-0001-8567-2049 http://dx.doi.org/10.7554/eLife.20937 eLife Creative Commons Attribution 4.0 International https://creativecommons.org/licenses/by/4.0/ application/pdf eLife Sciences Publications, Ltd eLife |
| spellingShingle | Shen, Zuolian Kang, Jinsuk Shakya, Arvind Tabaka, Marcin Jarboe, Elke A Regev, Aviv Tantin, Dean Enforcement of developmental lineage specificity by transcription factor Oct1 |
| title | Enforcement of developmental lineage specificity by transcription factor Oct1 |
| title_full | Enforcement of developmental lineage specificity by transcription factor Oct1 |
| title_fullStr | Enforcement of developmental lineage specificity by transcription factor Oct1 |
| title_full_unstemmed | Enforcement of developmental lineage specificity by transcription factor Oct1 |
| title_short | Enforcement of developmental lineage specificity by transcription factor Oct1 |
| title_sort | enforcement of developmental lineage specificity by transcription factor oct1 |
| url | http://hdl.handle.net/1721.1/111796 https://orcid.org/0000-0001-8567-2049 |
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