Post-translational regulation of the maternal-to-zygotic transition

Abstract

The maternal-to-zygotic transition (MZT) is essential for the developmental control handed from maternal products to newly synthesized zygotic genome in the earliest stages of embryogenesis, including maternal component (mRNAs and proteins) degradation and zygotic genome activation (ZGA). Various protein post-translational modifications have been identified during the MZT, such as phosphorylation, methylation and ubiquitination. Precise post-translational regulation mechanisms are essential for the timely transition of early embryonic development. In this review, we summarize recent progress regarding the molecular mechanisms underlying post-translational regulation of maternal component degradation and ZGA during the MZT and discuss some important issues in the field.

Keywords: Histone modification; MZT; Phosphorylation; Ubiquitination; ZGA.

Fig. 1

Overview of the maternal-to-zygotic transition in several model organisms. Dashed curves represent the degradation profiles of destabilized maternal component in each species. The solid line curves illustrate cumulatively increase in zygotic gene expression

Fig. 2

Mechanisms of post-translational regulation of maternal mRNA clearance. a PNG-mediated polyadenylation regulates smg mRNA translation. Cyclin B/CDK1-catalyzed phosphorylation on GNU inhibits the interaction between GNU and PNG–PLU, resulting in the inactivation of PNG kinase. Meiotic completion promotes GNU dephosphorylation and PNG kinase activation. The active PNG kinase phosphorylates PUM and one or more additional factors, which act in parallel through the smg mRNA’s 3′untranslated region (UTR) to promote the translation of Smaug. b ERK1/2 activates the translation of BTG4. Upon oocyte meiotic resumption, ERK1/2 is activated by upstream kinases and triggers CPEB1 phosphorylation and SCF^β-TrCP-dependent degradation. The phosphorylation and partial degradation of CPEB1 stimulates polyadenylation and translational activation of BTG4 to further promote maternal mRNA degradation by recruiting the RNA deadenylation complex CCR4-NOT. c Dephosphorylation of EDEN-BP regulates its deadenylation activity by deadenylase PARN and Cup. EDEN-BP is phosphorylated during oocyte maturation and calcium-dependently dephosphorylated following egg activation

Fig. 3

Emi2 regulates the activity of the APC/C to promote the metaphase II exit. Emi2 inhibits APC/C activity by binding the D-box receptor on the core of the APC/C and blocking the access of substrates to the APC/C. Upon fertilization, Ca2+-induced calmodulin kinase II (CaMKII) phosphorylates Emi2 and the phosphorylation of Emi2 can be recognized by the polo-box domain (PBD) of polo-like kinase 1 (Plx1) for further phosphorylation on the DSGX3S motif of Emi2. The phosphorylation of Emi2 is recognized by the Skp1–Cullin–F-box (SCF) ubiquitin ligase complex, which promotes its ubiquitination and further degradation to reactivate the APC/C

Fig. 4

Chromatin states and histone modification during ZGA. The global chromatin is more accessible during the early stages of embryogenesis, gradually changing to a more compact conformation. Local chromatin accessibility and transcription-related histone modifications appear during ZGA