scholarly journals Zygotic gene activation in mice: profile and regulation

Author(s):  
Fugaku AOKI
2018 ◽  
Vol 115 (29) ◽  
pp. E6780-E6788 ◽  
Author(s):  
Ken-ichiro Abe ◽  
Satoshi Funaya ◽  
Dai Tsukioka ◽  
Machika Kawamura ◽  
Yutaka Suzuki ◽  
...  

In mice, transcription initiates at the mid-one-cell stage and transcriptional activity dramatically increases during the two-cell stage, a process called zygotic gene activation (ZGA). Associated with ZGA is a marked change in the pattern of gene expression that occurs after the second round of DNA replication. To distinguish ZGA before and after the second-round DNA replication, the former and latter are called minor and major ZGA, respectively. Although major ZGA are required for development beyond the two-cell stage, the function of minor ZGA is not well understood. Transiently inhibiting minor ZGA with 5, 6-dichloro-1-β-d-ribofuranosyl-benzimidazole (DRB) resulted in the majority of embryos arresting at the two-cell stage and retention of the H3K4me3 mark that normally decreases. After release from DRB, at which time major ZGA normally occurred, transcription initiated with characteristics of minor ZGA but not major ZGA, although degradation of maternal mRNA normally occurred. Thus, ZGA occurs sequentially starting with minor ZGA that is critical for the maternal-to-zygotic transition.


2020 ◽  
Vol 21 (11) ◽  
pp. 4115 ◽  
Author(s):  
Isabel Gómez-Redondo ◽  
Priscila Ramos-Ibeas ◽  
Eva Pericuesta ◽  
Raúl Fernández-González ◽  
Ricardo Laguna-Barraza ◽  
...  

Minor splicing plays an important role in vertebrate development. Zrsr1 and Zrsr2 paralog genes have essential roles in alternative splicing, mainly participating in the recognition of minor (U12) introns. To further explore their roles during early embryo development, we produced Zrsr1mu and Zrsr2mu mutant mice, containing truncating mutations within the second zinc finger domain. Both homozygous mutant mice were viable with a normal lifespan. When we crossed a homozygous Zrsr2mu/mu female with Zrsr1mu/mu male, the double heterozygotes were non-viable, giving rise to embryos that stopped developing mainly between the 2- and 4-cell stages, just after zygotic gene activation. RNA-seq analysis of Zrsr1/2mu 2-cell embryos showed altered gene and isoform expression of thousands of genes enriched in gene ontology terms and biological pathways related to ribosome, RNA transport, spliceosome, and essential zygotic gene activation steps. Alternative splicing was analyzed, showing a significant increase in intron retention in both U2 and U12 intron-containing genes related to cell cycle and mitotic nuclear division. Remarkably, both Zrsr1 and Zrsr2 were required for the conversion of mouse-induced pluripotent stem cells into 2C-like cells. According to our results, Zrsr1 or Zrsr2 are necessary for ZGA and both are indispensable for the conversion of induced pluripotent stem cells into 2C-like cells.


2007 ◽  
Vol 53 (4) ◽  
pp. 707-715 ◽  
Author(s):  
Naojiro MINAMI ◽  
Toru SUZUKI ◽  
Satoshi TSUKAMOTO

EMBO Reports ◽  
2015 ◽  
Vol 16 (7) ◽  
pp. 803-812 ◽  
Author(s):  
Keisuke Aoshima ◽  
Erina Inoue ◽  
Hirofumi Sawa ◽  
Yuki Okada

2019 ◽  
Author(s):  
Woonyung Hur ◽  
Marco Tarzia ◽  
Victoria E. Deneke ◽  
Esteban A. Terzo ◽  
Robert J. Duronio ◽  
...  

SummaryMany membrane-less organelles form through liquid-liquid phase separation, but how their size is controlled and whether size is linked to function remain poorly understood. The Histone Locus Body (HLB) is an evolutionarily conserved nuclear body that regulates the transcription and processing of histone mRNAs. Here, we show that Drosophila HLBs form through phase separation of the scaffold protein multi-sex combs (Mxc). The size of HLBs is controlled in a precise and dynamic manner that is dependent on the cell cycle and zygotic gene activation. Control of HLB growth is achieved by a mechanism integrating nascent mRNAs at the histone locus, which catalyzes phase separation, and the nuclear concentration of Mxc, which is controlled by the activity of cyclin-dependent kinases. Reduced Cdk2 activity results in smaller HLBs and the appearance of nascent, misprocessed histone mRNAs. Our experiments thus identify a mechanism linking nuclear body growth and size with gene expression.


2020 ◽  
Author(s):  
Amanda L. Fry ◽  
Amy Webster ◽  
Rojin Chitrakar ◽  
L. Ryan Baugh ◽  
E. Jane Albert Hubbard

AbstractQuiescence, an actively-maintained reversible state of cell cycle arrest, is not well understood. PTEN is one of the most frequently lost tumor suppressors in human cancers and regulates quiescence of stem cells and cancer cells. In C. elegans mutant for daf-18, the sole C. elegans PTEN ortholog, primordial germ cells (PGCs) divide inappropriately in starvation conditions, in a TOR-dependent manner. Here, we further investigated the role of daf-18 in maintaining PGC quiescence. We found that maternal or zygotic daf-18 is sufficient to maintain cell cycle quiescence, that daf-18 acts in the germ line and soma, and that daf-18 affects timing of PGC divisions in fed animals. Importantly, our results also implicate daf-18 in zygotic germline gene activation, though not in germline fate specification. However, TOR is less important to zygotic germline gene expression, suggesting that in the absence of food daf-18/PTEN prevents inappropriate germline zygotic gene activation and cell division by distinct mechanisms.


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