Publikasjoner
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Skuland, Trine; Fosslie, Madeleine Lystad; Khodeer, Sherif; Alemu, Endalkachew Ashenafi; Johansen, Jens Vilstrup & Indahl, Marie
[Vis alle 12 forfattere av denne artikkelen]
(2025).
Broad H3K4me3 domains support oocyte genome silencing and maturation but are dispensable for repression in early embryos.
Development.
ISSN 0950-1991.
152(21),
s. 1–15.
doi:
10.1242/dev.204638.
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Epigenetic reprogramming and embryonic genome activation (EGA) are crucial events during early development. Establishment of distinctive broad histone H3 lysine 4 trimethylation (H3K4me3) domains in the oocyte is necessary for genome silencing, and their removal in the 2-cell embryo is crucial for EGA and development in mice. However, the stage-specific requirement for broad H3K4me3 domains is unclear. Here, we show that inducing broad H3K4me3 removal in mouse oocytes can relieve genome silencing, impair oocyte maturation timing, and may cause transcriptional reactivation in resulting parthenogenetic 1-cell embryos. We further demonstrate that broad H3K4me3 demethylation precedes EGA but, surprisingly, premature depletion in zygotes or early 2-cell embryos does not alter the transcriptional program. Our findings suggest that broad H3K4me3 domains are required for oocyte genome silencing, timely maturation and post-fertilisation silencing, but onward pre-EGA transcriptional repression is not dependent on the original mark. This work contributes to the understanding of events and mechanisms involved in genome silencing and activation in early development, providing insight into potential modes of failure that may contribute to infertility.
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Li, Yanjiao; Wang, Yunhao; Cengiz, Aylin; Jin, Kangxuan; castroviejo, Blanca Corral & Lin, Xiaolin
[Vis alle 19 forfattere av denne artikkelen]
(2025).
The RNA m6A landscape during human oocyte-to-embryo transition.
EMBO Journal.
ISSN 0261-4189.
44(14),
s. 4150–4180.
doi:
10.1038/s44318-025-00474-5.
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RNA N6-methyladenosine (m6A, m6A) modification is a critical regulator for a range of physiological processes. However, the dynamic m6A profiles within human preimplantation embryos remain uncharacterized. Here, we present the first RNA m6A landscape of single human oocytes and early embryos. Comparative analyses with mouse data reveal an intriguing divergence during the window of zygotic genome activation. m6A-modified genes are involved in regulation of gene transcription, while unmodified genes are mainly associated with basic metabolic processes. Maternal decay mRNAs exhibit a propensity for m6A modifications, and these genes are targeted by miRNAs. m6A modified genes that are constantly expressed across all stages demonstrate higher translation efficiency. Moreover, we observe frequent m6A enrichment on stage-specifically expressed retrotransposons, particularly within young subfamilies. m6A inhibitor leads to m6A erasure on massive retrotransposons. In summary, this study provides a resource to broaden our understanding about the regulatory roles of m6A during early human embryo development.
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Li, Yanjiao; Wang, Yunhao; Vera-Rodriguez, Maria; Lindeman, Leif Christopher; Skuggen, Linda Ellevog & Rasmussen, Erik Magne Koscielniak
[Vis alle 21 forfattere av denne artikkelen]
(2023).
Single-cell m6A mapping in vivo using picoMeRIP–seq.
Nature Biotechnology.
ISSN 1087-0156.
doi:
10.1038/s41587-023-01831-7.
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Abstract Current N 6 -methyladenosine (m 6 A) mapping methods need large amounts of RNA or are limited to cultured cells. Through optimized sample recovery and signal-to-noise ratio, we developed picogram-scale m 6 A RNA immunoprecipitation and sequencing (picoMeRIP–seq) for studying m 6 A in vivo in single cells and scarce cell types using standard laboratory equipment. We benchmark m 6 A mapping on titrations of poly(A) RNA and embryonic stem cells and in single zebrafish zygotes, mouse oocytes and embryos.
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Wang, Yunhao; Li, Yanjiao; Skuland, Trine; Zhou, Chengjie; Li, Aifu & Hashim, Adnan
[Vis alle 13 forfattere av denne artikkelen]
(2023).
The RNA m6A landscape of mouse oocytes and preimplantation embryos.
Nature Structural & Molecular Biology.
ISSN 1545-9993.
30(5),
s. 703–709.
doi:
10.1038/s41594-023-00969-x.
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Despite the significance of N6-methyladenosine (m6A) in gene regulation, the requirement for large amounts of RNA has hindered m6A profiling in mammalian early embryos. Here we apply low-input methyl RNA immunoprecipitation and sequencing to map m6A in mouse oocytes and preimplantation embryos. We define the landscape of m6A during the maternal-to-zygotic transition, including stage-specifically expressed transcription factors essential for cell fate determination. Both the maternally inherited transcripts to be degraded post fertilization and the zygotically activated genes during zygotic genome activation are widely marked by m6A. In contrast to m6A-marked zygotic ally-activated genes, m6A-marked maternally inherited transcripts have a higher tendency to be targeted by microRNAs. Moreover, RNAs derived from retrotransposons, such as MTA that is maternally expressed and MERVL that is transcriptionally activated at the two-cell stage, are largely marked by m6A. Our results provide a foundation for future studies exploring the regulatory roles of m6A in mammalian early embryonic development.
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Zhang, Zhichao; Manaf, Adeel; Li, Yanjiao; Pérez, Sonia Peña; Suganthan, Rajikala & Dahl, John Arne
[Vis alle 8 forfattere av denne artikkelen]
(2019).
Histone methylations define neural stem/progenitor cell subtypes in the mouse subventricular zone.
Molecular Neurobiology.
ISSN 0893-7648.
doi:
10.1007/s12035-019-01777-5.
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Neural stem/progenitor cells (NSPCs) persist in the mammalian brain throughout life and can be activated in response to the physiological and pathophysiological stimuli. Epigenetic reprogramming of NPSC represents a novel strategy for enhancing the intrinsic potential of the brain to regenerate after brain injury. Therefore, defining the epigenetic features of NSPCs is important for developing epigenetic therapies for targeted reprogramming of NSPCs to rescue neurologic function after injury. In this study, we aimed at defining different subtypes of NSPCs by individual histone methylations. We found the three histone marks, histone H3 lysine 4 trimethylation (H3K4me3), histone H3 lysine 27 trimethylation (H3K27me3), and histone H3 lysine 36 trimethylation (H3K36me3), to nicely and dynamically portray individual cell types during neurodevelopment. First, we found all three marks co-stained with NSPC marker SOX2 in mouse subventricular zone. Then, CD133, Id1, Mash1, and DCX immunostaining were used to define NSPC subtypes. Type E/B, B/C, and C/A cells showed high levels of H3K27me3, H3K36me3, and H3K4me3, respectively. Our results reveal defined histone methylations of NSPC subtypes supporting that epigenetic regulation is critical for neurogenesis and for maintaining NSPCs.
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Publisert
29. juli 2026 12:56
- Sist endret
29. juli 2026 12:56
