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...

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Main Authors: Edupuganti, Raghu Ram, Harikumar, Arigela, Aaronson, Yair, Biran, Alva, Sailaja, Badi Sri, Nissim-Rafinia, Malka, Azad, Gajendra Kumar, Cohen, Malkiel A., Park, Jung Eun, Shivalila, Chikdu S., Markoulaki, Styliani, Sze, Siu Kwan, Jaenisch, Rudolf, Meshorer, Eran
Other Authors: School of Biological Sciences
Format: Journal Article
Language:English
Published: 2017
Subjects:
Online Access:https://hdl.handle.net/10356/86534
http://hdl.handle.net/10220/44040
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author Edupuganti, Raghu Ram
Harikumar, Arigela
Aaronson, Yair
Biran, Alva
Sailaja, Badi Sri
Nissim-Rafinia, Malka
Azad, Gajendra Kumar
Cohen, Malkiel A.
Park, Jung Eun
Shivalila, Chikdu S.
Markoulaki, Styliani
Sze, Siu Kwan
Jaenisch, Rudolf
Meshorer, Eran
author2 School of Biological Sciences
author_facet School of Biological Sciences
Edupuganti, Raghu Ram
Harikumar, Arigela
Aaronson, Yair
Biran, Alva
Sailaja, Badi Sri
Nissim-Rafinia, Malka
Azad, Gajendra Kumar
Cohen, Malkiel A.
Park, Jung Eun
Shivalila, Chikdu S.
Markoulaki, Styliani
Sze, Siu Kwan
Jaenisch, Rudolf
Meshorer, Eran
author_sort Edupuganti, Raghu Ram
collection NTU
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.
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spelling ntu-10356/865342023-02-28T17:01:26Z 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 Cohen, Malkiel A. Park, Jung Eun Shivalila, Chikdu S. Markoulaki, Styliani Sze, Siu Kwan Jaenisch, Rudolf Meshorer, Eran School of Biological Sciences SET Embryonic Stem Cells 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. Published version 2017-11-15T03:34:29Z 2019-12-06T16:24:10Z 2017-11-15T03:34:29Z 2019-12-06T16:24:10Z 2017 Journal Article Edupuganti, R. R., Harikumar, A., Aaronson, Y., Biran, A., Sailaja, B. S., Nissim-Rafinia, M., et al. (2017). Alternative SET/TAFI Promoters Regulate Embryonic Stem Cell Differentiation. Stem Cell Reports, 9(4), 1291-1303. 2213-6711 https://hdl.handle.net/10356/86534 http://hdl.handle.net/10220/44040 10.1016/j.stemcr.2017.08.021 en Stem Cell Reports © 2017 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). 13 p. application/pdf
spellingShingle SET
Embryonic Stem Cells
Edupuganti, Raghu Ram
Harikumar, Arigela
Aaronson, Yair
Biran, Alva
Sailaja, Badi Sri
Nissim-Rafinia, Malka
Azad, Gajendra Kumar
Cohen, Malkiel A.
Park, Jung Eun
Shivalila, Chikdu S.
Markoulaki, Styliani
Sze, Siu Kwan
Jaenisch, Rudolf
Meshorer, Eran
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
topic SET
Embryonic Stem Cells
url https://hdl.handle.net/10356/86534
http://hdl.handle.net/10220/44040
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