Alternative SET/TAFI Promoters Regulate Embryonic Stem Cell Differentiation
Embryonic stem cells (ESCs) are regulated by pluripotency-related transcription factors in concert with chromatin regulators. To identify additional stem cell regulators, we screened a library of endogenously labeled fluorescent fusion proteins in mouse ESCs for fluorescence loss during differentiat...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
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Elsevier
2018
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| Online Access: | http://hdl.handle.net/1721.1/116605 https://orcid.org/0000-0002-2905-0306 |
| _version_ | 1826204154762100736 |
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| author | Edupuganti, Raghu Ram Harikumar, Arigela Aaronson, Yair Biran, Alva Sailaja, Badi Sri Nissim-Rafinia, Malka Azad, Gajendra Kumar Park, Jung Eun Markoulaki, Styliani Sze, Siu Kwan Meshorer, Eran Cohen, Malkiel A Shivalila, Chikdu Shakti Jaenisch, Rudolf |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Edupuganti, Raghu Ram Harikumar, Arigela Aaronson, Yair Biran, Alva Sailaja, Badi Sri Nissim-Rafinia, Malka Azad, Gajendra Kumar Park, Jung Eun Markoulaki, Styliani Sze, Siu Kwan Meshorer, Eran Cohen, Malkiel A Shivalila, Chikdu Shakti Jaenisch, Rudolf |
| author_sort | Edupuganti, Raghu Ram |
| collection | MIT |
| description | Embryonic stem cells (ESCs) are regulated by pluripotency-related transcription factors in concert with chromatin regulators. To identify additional stem cell regulators, we screened a library of endogenously labeled fluorescent fusion proteins in mouse ESCs for fluorescence loss during differentiation. We identified SET, which displayed a rapid isoform shift during early differentiation from the predominant isoform in ESCs, SETα, to the primary isoform in differentiated cells, SETβ, through alternative promoters. SETα is selectively bound and regulated by pluripotency factors. SET depletion causes proliferation slowdown and perturbed neuronal differentiation in vitro and developmental arrest in vivo, and photobleaching methods demonstrate SET's role in maintaining a dynamic chromatin state in ESCs. This work identifies an important regulator of pluripotency and early differentiation, which is controlled by alternative promoter usage. Keywords: pluripotency; embryonic stem cells; differentiation; SET; epigenetics; chromatin; histone dynamics; histone chaperone; TAF-I; TAFI |
| first_indexed | 2024-09-23T12:49:45Z |
| format | Article |
| id | mit-1721.1/116605 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T12:49:45Z |
| publishDate | 2018 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1166052022-10-01T11:21:52Z Alternative SET/TAFI Promoters Regulate Embryonic Stem Cell Differentiation Edupuganti, Raghu Ram Harikumar, Arigela Aaronson, Yair Biran, Alva Sailaja, Badi Sri Nissim-Rafinia, Malka Azad, Gajendra Kumar Park, Jung Eun Markoulaki, Styliani Sze, Siu Kwan Meshorer, Eran Cohen, Malkiel A Shivalila, Chikdu Shakti Jaenisch, Rudolf Massachusetts Institute of Technology. Department of Biology Cohen, Malkiel A Shivalila, Chikdu Shakti Jaenisch, Rudolf Embryonic stem cells (ESCs) are regulated by pluripotency-related transcription factors in concert with chromatin regulators. To identify additional stem cell regulators, we screened a library of endogenously labeled fluorescent fusion proteins in mouse ESCs for fluorescence loss during differentiation. We identified SET, which displayed a rapid isoform shift during early differentiation from the predominant isoform in ESCs, SETα, to the primary isoform in differentiated cells, SETβ, through alternative promoters. SETα is selectively bound and regulated by pluripotency factors. SET depletion causes proliferation slowdown and perturbed neuronal differentiation in vitro and developmental arrest in vivo, and photobleaching methods demonstrate SET's role in maintaining a dynamic chromatin state in ESCs. This work identifies an important regulator of pluripotency and early differentiation, which is controlled by alternative promoter usage. Keywords: pluripotency; embryonic stem cells; differentiation; SET; epigenetics; chromatin; histone dynamics; histone chaperone; TAF-I; TAFI National Institutes of Health (U.S.) (Grant HD045022) National Institutes of Health (U.S.) (Grant R37-CA084198) National Institutes of Health (U.S.) (Grant R01NS088538-01) 2018-06-26T13:57:20Z 2018-06-26T13:57:20Z 2017-09 2017-08 2018-06-25T19:59:52Z Article http://purl.org/eprint/type/JournalArticle 2213-6711 http://hdl.handle.net/1721.1/116605 Edupuganti, Raghu Ram et al. “Alternative SET/TAFI Promoters Regulate Embryonic Stem Cell Differentiation.” Stem Cell Reports 9, 4 (October 2017): 1291–1303 © 2017 The Authors https://orcid.org/0000-0002-2905-0306 http://dx.doi.org/10.1016/J.STEMCR.2017.08.021 Stem Cell Reports Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier Elsevier |
| spellingShingle | Edupuganti, Raghu Ram Harikumar, Arigela Aaronson, Yair Biran, Alva Sailaja, Badi Sri Nissim-Rafinia, Malka Azad, Gajendra Kumar Park, Jung Eun Markoulaki, Styliani Sze, Siu Kwan Meshorer, Eran Cohen, Malkiel A Shivalila, Chikdu Shakti Jaenisch, Rudolf Alternative SET/TAFI Promoters Regulate Embryonic Stem Cell Differentiation |
| title | Alternative SET/TAFI Promoters Regulate Embryonic Stem Cell Differentiation |
| title_full | Alternative SET/TAFI Promoters Regulate Embryonic Stem Cell Differentiation |
| title_fullStr | Alternative SET/TAFI Promoters Regulate Embryonic Stem Cell Differentiation |
| title_full_unstemmed | Alternative SET/TAFI Promoters Regulate Embryonic Stem Cell Differentiation |
| title_short | Alternative SET/TAFI Promoters Regulate Embryonic Stem Cell Differentiation |
| title_sort | alternative set tafi promoters regulate embryonic stem cell differentiation |
| url | http://hdl.handle.net/1721.1/116605 https://orcid.org/0000-0002-2905-0306 |
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