The acetyllysine reader BRD3R promotes human nuclear reprogramming and regulates mitosis.

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

Nature communications 2016

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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.

Citation

Zhicheng Shao, Ruowen Zhang, Alireza Khodadadi-Jamayran, Bo Chen, Michael R Crowley, Muhamad A Festok, David K Crossman, Tim M Townes, Kejin Hu. The acetyllysine reader BRD3R promotes human nuclear reprogramming and regulates mitosis. Nature communications. 2016;7:10869