The nuclear factor CECR2 promotes somatic cell reprogramming by reorganizing the chromatin structure.
The nuclear factor CECR2 promotes somatic cell reprogramming by reorganizing the chromatin structure.
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DOI：
10.1074/jbc.ra120.014598
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发表时间：
2021-01
期刊：
影响因子：
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通讯作者：
Liu J
中科院分区：
文献类型：
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作者：
Wu L;Zhao G;Xu S;Kuang J;Ming J;Wu G;Wang T;Wang B;Zhu P;Pei D;Liu J
体细胞可以用一组最少的确定因子Oct 3/4、Sox 2、Klf 4和c-Myc（也称为OKSM）重编程为多能干细胞，尽管这种重编程效率有点低。最近的工作已经确定了其他核因子，包括SALL 4，可以与OSK因子协同作用，以改善重编程动力学，但这些因子中的每一个的具体作用仍然知之甚少。在这项研究中，我们试图了解更多关于SALL 4的作用。我们观察到SALL 4是促进OKS诱导的重编程的最重要的因素。为了寻找SALL 4下游的分子，我们筛选了一组假定的靶点，以确定它们是否可以促进OKS诱导的重编程。我们确定了CECR 2，一个多结构域核因子和组蛋白乙酰赖氨酸阅读器，作为SALL 4效应器。从机制上讲，我们确定SALL 4通过直接结合其启动子区域来激活Cecr 2表达。CECR 2反过来通过形成染色质重塑复合物来促进重编程;该复合物包含SWI/SNF家族成员SMARCA 1，并且依赖于CECR 2的DTT结构域。总之，我们的研究结果表明，CECR 2是一种新的重编程因子，并通过蛋白质网络克服重编程过程中的表观遗传障碍。
Somatic cells can be reprogrammed into pluripotent stem cells with a minimal set of defined factors, Oct3/4, Sox2, Klf4, and c-Myc, also known as OKSM, although this reprogramming is somewhat inefficient. Recent work has identified other nuclear factors, including SALL4, that can synergize with the OSK factors to improve reprogramming dynamics, but the specific role of each of these factors remains poorly understood. In this study, we sought to learn more about the role of SALL4. We observed that SALL4 was the most significant factor in promoting OKS-induced reprogramming. To look for molecules downstream of SALL4, we screened a set of putative targets to determine whether they could promote OKS-induced reprogramming. We identified CECR2, a multidomain nuclear factor and histone acetyl-lysine reader, as a SALL4 effector. Mechanistically, we determined that SALL4 activates Cecr2 expression by directly binding to its promotor region. CECR2 in turn promotes reprogramming by forming a chromatin remodeling complex; this complex contained the SWI/SNF family member SMARCA1 and was dependent on CECR2’s DTT domain. In combination, our findings suggest that CECR2 is a novel reprogramming factor and works through a protein network to overcome epigenetic barriers during reprogramming.