Histone methyltransferase SETD2 is required for meiotic maturation in mouse oocyte

Li, Chunling; Diao, Feiyang; Qiu, Danhong; Jiang, Man-Xi; Li, Xiaoyan; Han, Longsen; Li, Ling; Hou, Xiaohong; Ge, Juan; Ou, Xiang‐Hong; Liu, Jiayin; Wang, Qiang

doi:10.1002/jcp.26836

Cited by 16 publications

(12 citation statements)

References 42 publications

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“…We then investigated the reproductive functions of the setd2-null zebrafish. In contrast to the previous findings that the mouse Setd2 is required for sperm and oocyte development 38,39,55 , and that the germ cell-specific Setd2 knockout mice are sterile 38,39 , we surprisingly observed that both male and female homozygous setd2-null zebrafish could produce a number of progenies, suggesting that their reproductive functions should remain intact. To clarify this issue closely, we examined the reproductive processes of the setd2-null zebrafish ranging from germ cell development to fertilization.…”

Section: Setd2-null Zebrafish Are Fertile In Both Male and Femalecontrasting

confidence: 99%

setd2 knockout zebrafish is viable and fertile: differential and developmental stress-related requirements for Setd2 and histone H3K36 trimethylation in different vertebrate animals

et al. 2020

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Setd2 is the only enzyme that catalyzes histone H3 lysine 36 trimethylation (H3K36me3) on virtually all actively transcribed protein-coding genes, and this mechanism is evolutionarily conserved from yeast to human. Despite this widespread and conserved activity, Setd2 and H3K36me3 are dispensable for normal growth of yeast but are absolutely required for mammalian embryogenesis, such as oocyte maturation and embryonic vasculogenesis in mice, raising a question of how the functional requirements of Setd2 in specific developmental stages have emerged through evolution. Here, we explored this issue by studying the essentiality and function of Setd2 in zebrafish. Surprisingly, the setd2-null zebrafish are viable and fertile. They show Mendelian birth ratio and normal embryogenesis without vascular defect as seen in mice; however, they have a small body size phenotype attributed to insufficient energy metabolism and protein synthesis, which is reversable in a nutrition-dependent manner. Unlike the sterile Setd2-null mice, the setd2-null zebrafish can produce functional sperms and oocytes. Nonetheless, related to the requirement of maternal Setd2 for oocyte maturation in mice, the second generation of setd2-null zebrafish that carry no maternal setd2 show decreased survival rate and a developmental delay at maternal-to-zygotic transition. Taken together, these results indicate that, while the phenotypes of the setd2-null zebrafish and mice are apparently different, they are matched in parallel as the underlying mechanisms are evolutionarily conserved. Thus, the differential requirements of Setd2 may reflect distinct viability thresholds that associate with intrinsic and/or extrinsic stresses experienced by the organism through development, and these epigenetic regulatory mechanisms may serve as a reserved source supporting the evolution of life from simplicity to complexity.

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Section: Setd2-null Zebrafish Are Fertile In Both Male and Femalecontrasting

confidence: 99%

setd2 knockout zebrafish is viable and fertile: differential and developmental stress-related requirements for Setd2 and histone H3K36 trimethylation in different vertebrate animals

et al. 2020

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“…When expressed in mammalian cells, a FLAG-tagged version of tSETD2 (tSETD2-FLAG) localized to the nucleus during interphase and was dispersed throughout mitotic cells (Fig. S1 & S2), similar to the localization of expressed full-length and endogenous SETD2 (30,31). Recombinant tSETD2-FLAG was purified from HEK293 cells, yielding a single species on size exclusion chromatography (Fig.…”

Section: Setd2 Methylates Tubulin In Vitromentioning

confidence: 85%

Molecular determinants for α-tubulin methylation by SETD2

Kearns

Mason

Rathmell

et al. 2021

Journal of Biological Chemistry

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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“…In oocytes, a significant positive correlation between transcription and highly methylated regions has been reported [17]. It is known that transcriptionally active regions are marked with H3K36me3 and that the histone methyltransferase SET domain containing 2 (SETD2) is responsible for the histone methylation in oocytes [18]. Since SETD2 is reported to interact with the phosphorylated C-terminal domain of RNA polymerase II (RNA pol II) [19], SETD2 appears to methylate histones at regions actively transcribed by the polymerase.…”

Section: Specification Of De Novo Dna Methylation Sitesmentioning

confidence: 99%

Recent Insights into the Mechanisms ofDe Novoand Maintenance of DNA Methylation in Mammals

Unoki¹

2020

DNA Methylation Mechanism

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DNA methylation is one of the key epigenetic mechanisms essential for transcriptional regulation, silencing of transposable elements, and genome stabilization. Under physiological conditions, DNA methylation is erased and then established genome-wide during gametogenesis and embryogenesis. De novo DNA methylation by the enzymatic reaction of the de novo DNA methyltransferases (DNMTs), DNMT3A and DNMT3B, occurs during the establishment of DNA methylation patterns specific to each germ cell type or somatic cell type after the erasure. Once cell type-specific DNA methylation patterns are established during embryogenesis, which can extend to early childhood, the maintenance of DNA methyltransferase DNMT1 and its cofactor UHRF1 cooperatively maintain the pattern throughout the individual's lifetime. Recently, our group found that UHRF1 is also involved in de novo DNA methylation during oogenesis. Moreover, our group has identified two genes, CDCA7 and HELLS, to be the causative genes of ICF syndrome, characterized by hypomethylation of centromeric and pericentromeric repetitive sequences. Because CDCA7/HELLS comprise a chromatin remodeling complex, there are evidently certain regions where chromatin remodeling is required to achieve maintenance of DNA methylation. In this chapter, the current situation with respect to our understanding of de novo and maintenance of DNA methylation mechanisms under physiological conditions in mammals is summarized.

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Histone methyltransferase SETD2 is required for meiotic maturation in mouse oocyte

Cited by 16 publications

References 42 publications

setd2 knockout zebrafish is viable and fertile: differential and developmental stress-related requirements for Setd2 and histone H3K36 trimethylation in different vertebrate animals

setd2 knockout zebrafish is viable and fertile: differential and developmental stress-related requirements for Setd2 and histone H3K36 trimethylation in different vertebrate animals

Molecular determinants for α-tubulin methylation by SETD2

Recent Insights into the Mechanisms ofDe Novoand Maintenance of DNA Methylation in Mammals

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