基金ACKNOWLEDGEMENTS We apologize to colleagues whose work could not be cited due to the scope of this review. We would like to thank members in Yan laboratory for discussions. We thank Brendan Lehnert, Xinlei Sheng, Quanxiu Li, Dan Ma and Xinhui Zhou for critical reading. This work was supported by funds from the National Basic Research Program (973 Program) (No. 2011CB910501), the National Natural Science Foundation of China (Grant Nos. 31321062-20131319400, 31125009, and 91017011 ), and funds from Tsinghua-Peking Center for Life Sciences. The research of N.Y. was supported in part by an International Early Career Scientist grant from the Howard Hughes Medical Institute.