CRL4 Complex Regulates Mammalian Oocyte Survival and Reprogramming by Activation of TET Proteins

时间:2013年12月20日 访问次数:3158

Science. 2013 Dec 20; 342(6165):1518-21.

Chao Yu, Yin-Li Zhang, Wei-Wei Pan, Xiao-Meng Li, Zhong-Wei Wang, Zhao-Jia Ge, Jian-Jie Zhou, Yong Cang, Chao Tong, Qing-Yuan Sun* , Heng-Yu Fan*


The duration of a woman’s reproductive period is determined by the size and persistence of a dormant oocyte pool. Specific oocyte genes are essential for follicle maintenance and female fertility. The mechanisms that regulate the expression of these genes are poorly understood. We found that a cullin-ring finger ligase-4 (CRL4) complex was crucial in this process. Oocyte-specific deletion of the CRL4 linker protein DDB1 or its substrate adaptor VPRBP (also known as DCAF1) caused rapid oocyte loss, premature ovarian insufficiency, and silencing of fertility maintaining genes. CRL4VPRBP activates the TET methylcytosine dioxygenases, which are involved in female germ cell development and zygote genome reprogramming. Hence, CRL4VPRBP ubiquitin ligase is a guardian of female reproductive life in germ cells and a maternal reprogramming factor after fertilization.