Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Institute of Plant and Microbial Biology, Academia Sinica, Taipei 11529, Taiwan.
Stem Cell Reports. 2018 Jan 9;10(1):243-256. doi: 10.1016/j.stemcr.2017.11.020. Epub 2017 Dec 28.
Transition from primed to naive pluripotency is associated with dynamic changes in transposable element (TE) expression and demethylation of imprinting control regions (ICRs). In mouse, ICR methylation and TE expression are each regulated by TRIM28; however, the role of TRIM28 in humans is less clear. Here, we show that a null mutation in TRIM28 causes significant alterations in TE expression in both the naive and primed states of human pluripotency, and phenotypically this has limited effects on self-renewal, instead causing a loss of germline competency. Furthermore, we discovered that TRIM28 regulates paternal ICR methylation and chromatin accessibility in the primed state, with no effects on maternal ICRs. Taken together, our study shows that abnormal TE expression is tolerated by self-renewing human pluripotent cells, whereas germline competency is not.
从初始状态到幼稚状态的多能性转变与转座元件 (TE) 表达和印迹控制区 (ICR) 去甲基化的动态变化有关。在小鼠中，ICR 甲基化和 TE 表达都受到 TRIM28 的调节；然而，TRIM28 在人类中的作用还不太清楚。在这里，我们表明 TRIM28 的缺失突变导致人类多能性的幼稚和初始状态下 TE 表达的显著改变，表型上这对自我更新的影响有限，反而导致生殖系能力的丧失。此外，我们发现 TRIM28 在初始状态下调节父系 ICR 甲基化和染色质可及性，而对母系 ICR 没有影响。总之，我们的研究表明，异常的 TE 表达可以被自我更新的人类多能细胞所容忍，而生殖系能力则不能。
