Alternative SET/TAFI Promoters Regulate Embryonic Stem Cell Differentiation

作者：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^*

来源：Stem Cell Reports, 2017, 9(4): 1291-1303.

DOI：10.1016/j.stemcr.2017.08.021

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, SET alpha, to the primary isoform in differentiated cells, SET beta, through alternative promoters. SETa 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.

• 出版日期2017-10-10
• 单位南阳理工学院