CRL4 < sup > DCAF13 < /sup > E3 ubiquitin ligase targets MeCP2 for degradation to prevent DNA hypermethylation and ensure normal transcription in growing oocytes

In this study, we found MeCP2 protein was highly expressed in primordial and primary follicle, but was almost undetectable in secondary follicles. However, in aged ovary, MeCP2 protein is significantly increased in both oocyte and granulosa cells. Overexpression of MeCP2 in growing oocyte caused transcription dysregulation, DNA hypermethylation, and genome instability, ultimately leading to follicle growth arrest and apoptosis. MeCP2 is targeted by DCAF13, a substrate recognition adaptor of the Cullin 4-RING (CRL4) E3 ligase, and polyubiquitinated for degradation in both cells and oocytes. Dcaf13-null oocyte exhibited an accumulation of MeCP2 protein, and the partial rescue of follicle growth arrest induced by Dcaf13 deletion was observed following MeCP2 knockdown. The RNA-seq results revealed that large amounts of genes were regulated by the DCAF13-MeCP2 axis in growing oocytes. Our study demonstrated that CRL4DCAF13 E3 ubiquitin ligase targets MeCP2 for degradation to ensure normal DNA methylome and transcription in growing oocytes. Moreover, in aged ovarian follicles, deceased DCAF13 and DDB1 protein were observed, indicating a potential novel mechanism that regulates ovary aging.PMID:38578457 | PMC:PMC10997554 | DOI:10.1007/s00018-024-05185-4

Source: Cellular and Molecular Life Sciences : CMLS - April 5, 2024 Category: Cytology Authors: Peipei Ren Xiaomei Tong Junjian Li Huifang Jiang Siya Liu Xiang Li Mengru Lai Weijie Yang Yan Rong Yingyi Zhang Jiamin Jin Yerong Ma Weiwei Pan Heng-Yu Fan Songying Zhang Yin-Li Zhang Source Type: research