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Mechanisms regulating zygotic genome activation

Abstract

Following fertilization, the two specified gametes must unite to create an entirely new organism. The genome is initially transcriptionally quiescent, allowing the zygote to be reprogrammed into a totipotent state. Gradually, the genome is activated through a process known as the maternal-to-zygotic transition, which enables zygotic gene products to replace the maternal supply that initiated development. This essential transition has been broadly characterized through decades of research in several model organisms. However, we still lack a full mechanistic understanding of how genome activation is executed and how this activation relates to the reprogramming of the zygotic chromatin architecture. Recent work highlights the central role of transcriptional activators and suggests that these factors may coordinate transcriptional activation with other developmental changes.

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Fig. 1: New technologies enable precise detection of ZGA.
Fig. 2: ZGA is conserved across animals.
Fig. 3: Several mechanisms contribute to the timing of ZGA.
Fig. 4: Chromatin is reprogrammed during ZGA.

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Acknowledgements

The authors thank members of the Harrison laboratory and the reviewers for helpful feedback on the manuscript. K.N.S. was supported in part by the National Institutes of Health (NIH) National Research Service award T32 GM007215. M.M.H. was supported by grant R01GM11694 from the National Institute of General Medical Sciences and a Vallee Scholar Award.

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Nature Reviews Genetics thanks B. Cairns, K. Kuznetsova, N. Vastenhouw and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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Glossary

Totipotent

The property of a cell with the capacity to form all the cells of an organism, including extra-embryonic tissues.

Zygotic

Relating to the diploid, fertilized egg cell (zygote) that results from the fusion of an egg and a sperm.

Germ layers

The three layers of cells (ectoderm, mesoderm and endoderm) that are formed during gastrulation in the early embryo and differentiate to give rise to all the organs and tissues of the body.

Chromatin

The complex of DNA, RNA and protein that makes up the chromosomes of eukaryotes.

Cleavage divisions

The rapid, modified cell cycles of the early embryo that consist of only M (mitosis) and S (replication) phases and omit the G1 and G2 gap phases. These cycles occur in the absence of cell growth and therefore result in no change in the size of the embryo.

Nucleocytoplasmic ratio

(N:C ratio). The ratio of the nuclear content to the cytoplasmic content in a cell or embryo.

Polyspermic

Refers to an egg that has been fertilized by more than one sperm and thus contains three or more copies of each chromosome.

Haploid

Characterized by a single set of chromosomes. Most animals have diploid somatic cells (with two paired sets of chromosomes) but produce haploid gametes.

Compound chromosomes

Chromosomes formed by the attachment of two homologues through a single centromere that are therefore inherited together through mitosis and meiosis. They can be used to generate embryos deficient for an entire chromosome.

Protamines

Small, basic proteins that are used in the place of histones to help package DNA in the sperm of some species.

Demethylation

The process by which a demethylase enzyme removes a methyl group from a molecule.

Transposable elements

DNA sequences that can move from one position within the genome to another.

Topologically associating domains

(TADs). 3D chromosome structures within which DNA regions physically interact with each other more frequently than with regions outside.

MERVL

A family of endogenous retroviruses expressed in mouse embryos during zygotic genome activation. The human version is known as HERVL.

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Schulz, K.N., Harrison, M.M. Mechanisms regulating zygotic genome activation. Nat Rev Genet 20, 221–234 (2019). https://doi.org/10.1038/s41576-018-0087-x

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