Sin3a regulates the developmental progression through morula‐to‐blastocyst transition via Hdacl

Abstract

Suppressor interacting 3a (Sin3a) is a scaffold component of the chromatin repressive complex Sin3/histone deacetylase (Hdac). Sin3a has been shown as a hub gene driving preimplantation development in both mice and humans. However, its precise functions during preimplantation development remain unclear. Here, we show that the embryos arrested at morula stage upon specific depletion of Sin3a in mouse early embryos. Given the reduced cell number in Sin3a‐depleted embryos, blocked cell proliferation is observed, likely because of the increased level of Trp53 acetylation at lysine 379. Moreover, we found that Sin3a depletion reduces Cdx2 and Tir Na Nog (Nanog), suggesting a failure of the first cell fate decision. In addition, we noted a striking increase of genome‐wide DNA methylation, likely attributed to the increased nuclear DNA methyltransferase 1 observed in Sin3a‐depleted embryos. Notably, RNA sequencing analyses showed 717 genes are differentially expressed, and Gene Ontology analysis of down‐regulated genes (e.g., Hdac1) revealed top enriched terms involving protein deacetylation. Consistently, we confirmed a significant decrease of Hdac1 mRNA and protein abundance. Importantly, the development and Trp53 acetylation in Sin3a‐depleted embryos could be rescued by expression of Hdac1 but not Hdac2. In summary, our results indicate a vital role of Sin3a in safeguarding the developmental progression through the morula‐to‐blastocyst transition via Hdacl.—Zhao, P., Li, S., Wang, H., Dang, Y., Wang, L., Liu, T., Wang, S., Li, X., Zhang, K. Sin3a regulates the developmental progression through morula‐to‐blastocyst transition via Hdac1. FASEB J. 33, 12541–12553 (2019). http://www.fasebj.org

SIN3A Regulates Porcine Early Embryonic Development by Modulating CCNB1 Expression

“…The phenotypes described above is far more severe than the one we observed for mouse embryos ( Zhao et al, 2019 ), raising the possibility that SIN3A plays a species-specific role during early embryonic development. To further test this possibility, we then examined the functional role of SIN3A using bovine model.…”

“…Inhibition of Sin3a expression via RNAi during oocyte maturation leads to developmental arrest at the two-cell stage and global gene expression profile is disturbed ( Jimenez et al, 2015 ). We also found Sin3a deficiency in mouse early embryos causes embryonic block at morula stage, which is mediated through regulation of Hdac1 ( Zhao et al, 2019 ). Nonetheless, the functional requirement for SIN3A has been primarily conducted in murine model and has not been addressed in other species, including domestic animals.…”

“…SIN3A is expressed abundantly in mouse oocytes and early embryos ( Jimenez et al, 2015 ; Zhao et al, 2019 ). Single-cell RNA-seq analyses further revealed that it is a hub gene of the transcriptome networks in both mouse and human preimplantation embryos, suggesting a key functional role ( Xue et al, 2013 ).…”

The nucleolar protein NOP2 is required for nucleolar maturation and ribosome biogenesis during preimplantation development in mammals

“…The protocol was employed as we described previously . Mouse breeding was conducted under a 12 hours light/12 hours dark cycle.…”

“…The protocol was employed as we described previously. 17 Mouse breeding was conducted under a 12 hours light/12 hours dark cycle. Female mice aged 8-10 weeks (C57BL/6 × DBA2, B6D2; Beijing Vital River Laboratory Animal Technology, China) were superovulated by consecutive injections of 10 IU PMSG (Sansheng Biological Technology, Ningbo, China) and 10 IU human chorionic conservation of NOP2 in mammals.…”