The acetyllysine reader BRD3R promotes human nuclear reprogramming and regulates mitosis

乙酰赖氨酸阅读蛋白BRD3R促进人类核重编程并调控有丝分裂

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作者:Zhicheng Shao,Ruowen Zhang,Alireza Khodadadi-Jamayran,Bo Chen,Michael R Crowley,Muhamad A Festok,David K Crossman,Tim M Townes,Kejin Hu

Abstract

It is well known that both recipient cells and donor nuclei demonstrate a mitotic advantage as observed in the traditional reprogramming with somatic cell nuclear transfer (SCNT). However, it is not known whether a specific mitotic factor plays a critical role in reprogramming. Here we identify an isoform of human bromodomain-containing 3 (BRD3), BRD3R (BRD3 with Reprogramming activity), as a reprogramming factor. BRD3R positively regulates mitosis during reprogramming, upregulates a large set of mitotic genes at early stages of reprogramming, and associates with mitotic chromatin. Interestingly, a set of the mitotic genes upregulated by BRD3R constitutes a pluripotent molecular signature. The two BRD3 isoforms display differential binding to acetylated histones. Our results suggest a molecular interpretation for the mitotic advantage in reprogramming and show that mitosis may be a driving force of reprogramming.

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