Heng-Yu Fan’s team finds a novel factor DCAF13 which maintains the high pluripotency of preimplantation embryos

编辑: Date:2018/08/22

Astudy entitled "DCAF13 promotes pluripotency by negatively regulatingSUV39H1 stability during early embryonic development" was published onlinein the EMBO Journal on August 15, 2018. This work was finished by Prof. Heng-YuFan Lab at Life Sciences Institute, Zhejiang University. The core of this workis finding the mechanism of DCAF13 endowing high development potential of earlyembryos. Mechanistically, DCAF13 targets SUV39H1 for polyubiquitination andproteasomal degradation and therefore facilitates zygotic gene expression.

Fertilizationtriggers early preimplantation development of mammalian embryos, associatedwith chromatin reorganization. In comparison to somatic cell nuclear transfer(SCNT) and induced pluripotent stem cell (iPSC) reprogramming, early embryoshave a higher developmental potentiality. Previous studies have shown thatSUV39H1 is a major barrier for efficient reprogramming in both SCNT and iPSC.It’s a mystery whether SUV39H1 is involved in high potential of preimplantationembryonic reprogramming and how SUV39H1 activity is regulated during earlyembryo development.


Theyreport DCAF13 as a novel CRL4 adaptor is a highly expressed zygotic gene inboth murine and human embryos. Dcaf13 knockout murine embryos are arrested at the morula stage, accompanied withdecreased activities of rDNA transcription in eight-cell embryos. Furthermore,the overexpression of SUV39H1 in embryos mimics the phenotype of Dcaf13 knockout embryos. Consistently,biochemical assays show that DCAF13 bridges CRL4 E3 ubiquitin ligase to targetSUV39H1 for polyubiquitination and proteasomal degradation, and thereforefacilitates H3K9me3 removal and zygotic gene expression from eight-cell stage.These results indicate a novel factor for maintaining preimplantation embryonicdevelopment, and reveal underlying molecular mechanisms of preimplantationembryonic efficient reprogramming.

Link: http://emboj.embopress.org/content/early/2018/08/14/embj.201898981