Alternative SET/TAFI Promoters Regulate Embryonic Stem Cell Differentiation
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Author(s)
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
Date Issued
September 2017
Journal
Stem Cell Reports
Publisher
Elsevier
Citation
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
Version
Final published version
Abstract
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
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/J.STEMCR.2017.08.021
