Noncanonical Nucleotides in the Genome Around the Maternal‐Zygotic Transition

Kazzazy, Latifa and Mező, Dávid and Nagy, Kinga K. and Perey‐Simon, Viktória and Tóth, Judit and Békési, Angéla and Vértessy, Beáta and Varga, Máté (2025) Noncanonical Nucleotides in the Genome Around the Maternal‐Zygotic Transition. JOURNAL OF EXPERIMENTAL ZOOLOGY PART B: MOLECULAR AND DEVELOPMENTAL EVOLUTION. ISSN 1552-5007 (In Press)

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Abstract

From the very moment of fertilization and throughout development, the cells of animal embryos have to continuously orchestrate the dynamic reorganization of their epigenetic landscapes. One of the earliest major events of this reorganization occurs during the time of the maternal‐zygotic transition (MZT), when the control of the developmental process gradually shifts from maternal factors (initially present within the oocytes) to the genes of the embryo itself. As maternal transcripts and proteins are degraded, parental epigenetic information is often erased, and pioneer factors will turn on the transcriptional activity of the zygotic genome. This activation also coincides with the decompaction of the chromatin, which is essential for the successful initiation of gene expression in the zygote. Interestingly, in the past decades numerous studies reported findings that supported the role of noncanonical nucleotides in the process of MZT. These nucleobase moieties in these noncanonical nucleotides are covalently modified versions of the canonical bases, and often show a very dynamic presence within the genome. While most of the recent studies have deciphered in great detail the epigenetic role of methylcytosine and its derivates, other Noncanonical bases have received less attention. Here we suggest that the incorporation of nucleotides from deoxyuridine‐triphosphate (dUTP) or 6‐methyl‐ deoxyadenine‐triphosphate (6m‐dATP) into the genome is not mere noise or replication error but serves a well‐defined purpose: to aid chromatin decompaction through the timely induction of DNA repair pathways.

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