Shao Zhicheng, Zhang Ruowen, Khodadadi-Jamayran Alireza, Chen Bo, Crowley Michael R, Festok Muhamad A, Crossman David K, Townes Tim M, Hu Kejin
Stem Cell Institute, Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, Alabama 35294-0024, USA.
Department of Genetics, Howell and Elizabeth Heflin Center for Genomic Science, University of Alabama at Birmingham, Birmingham, Alabama 35294-0024, USA.
Nat Commun. 2016 Mar 7;7:10869. doi: 10.1038/ncomms10869.
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.
众所周知，在传统的体细胞核移植（SCNT）重编程过程中，受体细胞和供体细胞核均表现出有丝分裂优势。然而，尚不清楚是否有特定的有丝分裂因子在重编程中起关键作用。在此，我们鉴定出人类含溴结构域蛋白3（BRD3）的一种异构体BRD3R（具有重编程活性的BRD3）作为一种重编程因子。BRD3R在重编程过程中正向调节有丝分裂，在重编程早期上调大量有丝分裂基因，并与有丝分裂染色质相关联。有趣的是，由BRD3R上调的一组有丝分裂基因构成了多能性分子特征。这两种BRD3异构体对乙酰化组蛋白表现出不同的结合。我们的结果为重编程中的有丝分裂优势提供了一种分子解释，并表明有丝分裂可能是重编程的驱动力。
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