After fertilization, remodeling of the oocyte and sperm genomes is essential to convert these highly differentiated and transcriptionally quiescent cells into early cleavage-stage blastomeres that are transcriptionally active and totipotent. This developmental transition is accompanied by cell cycle adaptation, such as lengthening or shortening of the gap phases G1 and G2. However, regulation of these cell cycle changes is poorly understood, especially in mammals. Checkpoint kinase 1 (CHK1) is a protein kinase that regulates cell cycle progression in somatic cells. Here, we show that CHK1 regulates cell cycle progression in early mouse embryos by restraining CDK1 kinase activity due to CDC25A phosphatase degradation. CHK1 kinase also ensures the long G2 phase needed for genome activation and reprogramming gene expression in two-cell stage mouse embryos. Finally, Chk1 depletion leads to DNA damage and chromosome segregation errors that result in aneuploidy and infertility.

• Klíčová slova
• CDC25A phosphatase, CDK1 kinase, CHK1 kinase, cell cycle regulation, early mouse embryos,
• Publikační typ
• časopisecké články MeSH

The oocyte-to-embryo transition (OET) arguably initiates with formation of a primordial follicle and culminates with reprogramming of gene expression during the course of zygotic genome activation. This transition results in converting a highly differentiated cell, i.e. oocyte, to undifferentiated cells, i.e. initial blastomeres of a preimplantation embryo. A plethora of changes occur during the OET and include, but are not limited to, changes in transcription, chromatin structure, and protein synthesis; accumulation of macromolecules and organelles that will comprise the oocyte's maternal contribution to the early embryo; sequential acquisition of meiotic and developmental competence to name but a few. This review will focus on transcriptional and post-transcriptional changes that occur during OET in mouse because such changes are likely the major driving force for OET. We often take a historical and personal perspective, and highlight how advances in experimental methods often catalyzed conceptual advances in understanding the molecular bases for OET. We also point out questions that remain open and therefore represent topics of interest for future investigation.

• MeSH
• buněčná diferenciace fyziologie   MeSH
• embryonální vývoj fyziologie   MeSH
• genom MeSH
• myši MeSH
• oocyty fyziologie   MeSH
• ovariální folikul fyziologie   MeSH
• vývojová regulace genové exprese MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, N.I.H., Intramural MeSH

Loss of totipotentcy in an early embryo is directed by molecular processes responsible for cell fate decisions. Three dimensional genome organisation is an important factor linking chromatin architecture with stage specific gene expression patterns. Little is known about the role of chromosome organisation in gene expression regulation of lineage specific factors in mammalian embryos. Using bovine embryos as a model we have described these interactions at key developmental stages. Three bovine chromosomes (BTA) that differ in size, number of carried genes, and contain loci for key lineage regulators OCT4, NANOG and CDX2, were investigated. The results suggest that large chromosomes regardless of their gene density (BTA12 gene-poor, BTA5 gene-rich) do not significantly change their radial position within the nucleus. Gene loci however, may change its position within the chromosome territory (CT) and relocate its periphery, when stage specific process of gene activation is required. Trophectoderm specific CDX2 and epiblast precursor NANOG loci tend to locate on the surface or outside of the CTs, at stages related with their high expression. We postulate that the observed changes in CT shape reflect global alternations in gene expression related to differentiation.

• MeSH
• buněčné jádro genetika   MeSH
• buněčný rodokmen MeSH
• embryonální vývoj MeSH
• hybridizace in situ fluorescenční MeSH
• nanog genetika   metabolismus   MeSH
• oktamerní transkripční faktor 3 genetika   metabolismus   MeSH
• savčí chromozomy genetika   MeSH
• skot MeSH
• transkripční faktor CDX2 genetika   metabolismus   MeSH
• vývojová regulace genové exprese MeSH
• zvířata MeSH
• Check Tag
• skot MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• nanog MeSH
• oktamerní transkripční faktor 3 MeSH
• transkripční faktor CDX2 MeSH

Initiation of zygotic transcription in mammals is poorly understood. In mice, zygotic transcription is first detected shortly after pronucleus formation in 1-cell embryos, but the identity of the transcribed loci and mechanisms regulating their expression are not known. Using total RNA-Seq, we have found that transcription in 1-cell embryos is highly promiscuous, such that intergenic regions are extensively expressed and thousands of genes are transcribed at comparably low levels. Striking is that transcription can occur in the absence of defined core-promoter elements. Furthermore, accumulation of translatable zygotic mRNAs is minimal in 1-cell embryos because of inefficient splicing and 3' processing of nascent transcripts. These findings provide novel insights into regulation of gene expression in 1-cell mouse embryos that may confer a protective mechanism against precocious gene expression that is the product of a relaxed chromatin structure present in 1-cell embryos. The results also suggest that the first zygotic transcription itself is an active component of chromatin remodeling in 1-cell embryos.

• Klíčová slova
• RNA‐Seq, gene expression, preimplantation mouse embryo, pre‐mRNA splicing, transcription,
• MeSH
• 3' nepřekládaná oblast fyziologie   MeSH
• chromatin metabolismus   MeSH
• embryo savčí cytologie   metabolismus   MeSH
• genetická transkripce fyziologie   MeSH
• myši MeSH
• restrukturace chromatinu fyziologie   MeSH
• sestřih RNA fyziologie   MeSH
• vývojová regulace genové exprese fyziologie   MeSH
• zvířata MeSH
• zygota cytologie   metabolismus   MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• 3' nepřekládaná oblast MeSH
• chromatin MeSH

RNA silencing is a complex of mechanisms that regulate gene expression through small RNA molecules. The microRNA (miRNA) pathway is the most common of these in mammals. Genome-encoded miRNAs suppress translation in a sequence-specific manner and facilitate shifts in gene expression during developmental transitions. Here, we discuss the role of miRNAs in oocyte-to-zygote transition and in the control of pluripotency. Existing data suggest a common principle involving miRNAs in defining pluripotent and differentiated cells. RNA silencing pathways also rapidly evolve, resulting in many unique features of RNA silencing in different taxonomic groups. This is exemplified in the mouse model of oocyte-to-zygote transition, in which the endogenous RNA interference pathway has acquired a novel role in regulating protein-coding genes, while the miRNA pathway has become transiently suppressed.

• MeSH
• fylogeneze MeSH
• lidé MeSH
• malá interferující RNA genetika   metabolismus   MeSH
• mikro RNA klasifikace   genetika   metabolismus   MeSH
• molekulární sekvence - údaje MeSH
• oocyty cytologie   fyziologie   MeSH
• pluripotentní kmenové buňky cytologie   fyziologie   MeSH
• RNA interference * MeSH
• sekvence nukleotidů MeSH
• sekvenční seřazení MeSH
• zvířata MeSH
• zygota cytologie   fyziologie   MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• malá interferující RNA MeSH
• mikro RNA MeSH