Maternal Sall4 Is Indispensable for Epigenetic Maturation of Mouse Oocytes

Abstract

Sall4 (Splat-like 4) plays important roles in maintaining pluripotency of embryonic stem cells and in various developmental processes. Here, we find that Sall4 is highly expressed in oocytes and early embryos. To investigate the roles of SALL4 in oogenesis, we generated Sall4 maternal specific knock-out mice by using CRISPR/Cas9 system, and we find that the maternal deletion of Sall4 causes developmental arrest of oocytes at germinal vesicle stage with non-surrounded nucleus, and the subsequent meiosis resumption is prohibited. We further discover that the loss of maternal Sall4 causes failure in establishment of DNA methylation in oocytes. Furthermore, we find that Sall4 modulates H3K4me3 and H3K27me3 modifications by regulating the expression of key histone demethylases coding genes Kdm5b, Kdm6a, and Kdm6b in oocytes. Moreover, we demonstrate that the aberrant H3K4me3 and H3K27me3 cause mis-expression of genes that are critical for oocytes maturation and meiosis resumption. Taken together, our study explores a pivotal role of Sall4 in regulating epigenetic maturation of mouse oocytes.

Desiccation and supra‐zero temperature storage of cat germinal vesicles lead to less structural damage and similar epigenetic alterations compared to cryopreservation

“…What influence does lower H3K4me3 have on the oocyte? In murine oocytes, decreased H3K4me3 level has been linked to misexpression of genes essential for meiotic resumption, leading to failure to maturation (Xu, Chen et al, ; C. Yu et al, ). Consistent with its role in promoting oocyte maturation, increased H3K4me3 was associated with improving meiotic and developmental competence of porcine oocytes (X. X. Yu et al, ).…”

“…What influence does lower H3K4me3 have on the oocyte? In murine oocytes, decreased H3K4me3 level has been linked to misexpression of genes essential for meiotic resumption, leading to failure to maturation (Xu, Chen et al, 2017;C. Yu et al, 2017).…”

Beyond accessibility: ATAC-seq footprinting unravels kinetics of transcription factor binding during zygotic genome activation

“…For example, within the non-correlated cluster 13 TFs were identified which are of putative maternal origin 22 including SALL4. In mice, Sall4 protein is maternally contributed to the zygote, subsequently degraded at 2C and then reexpressed after zygotic transcription has initiated 26 . Consistent with this, SALL4 expression increases dramatically from 8C onwards (Supp.…”

Deletion of BAF250a affects oocyte epigenetic modifications and embryonic development

“…It has been reported that histone modifications can regulate the establishment of DNA methylation in the early embryo (Cedar & Bergman, 2009; Hatanaka et al, 2015; Ooi et al, 2007). Aberrant histone modifications can result in impaired oocyte maturation or abnormal embryonic development (Andreu‐Vieyra et al, 2010; Baumann, Viveiros, & De la Fuente, 2010; Hanna et al, 2018; Sha et al, 2018; Xu et al, 2017; Yu et al, 2017). Therefore, epigenetic changes are critical for the acquisition of developmental competence of oocytes.…”