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GEO help: Mouse over screen elements for information. |
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Status |
Public on Oct 18, 2023 |
Title |
A maternal-effect Padi6 variant causes nuclear and cytoplasmic abnormalities in oocytes as well as failure of epigenetic reprogramming and zygotic genome activation in embryos [WGS] |
Organism |
Mus musculus |
Experiment type |
Other
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Summary |
Maternal inactivation of genes encoding components of the sub-cortical maternal complex (SCMC) and its associated member PADI6 generally results in early embryo lethality. In humans, SCMC gene variants were found in the healthy mothers of children affected by multi-locus imprinting disturbances (MLID). However, how the SCMC controls the DNA methylation required to regulate imprinting remains poorly defined. We generated a mouse line carrying a Padi6 missense variant that was identified in a family with Beckwith-Wiedemann syndrome and MLID. If homozygous in female mice this variant resulted in interruption of embryo development at the 2-cell stage. Single-cell multi-omic analyses demonstrated defective maturation of Padi6-mutant oocytes and incomplete DNA demethylation, down-regulation of zygotic genome activation (ZGA) genes, up-regulation of maternal decay genes and developmental delay in 2-cell embryos developing from Padi6-mutant oocytes, but little effect on genomic imprinting. Western blotting and immunofluorescence analyses showed reduced level of UHRF1 in oocytes and abnormal localization of DNMT1 and UHRF1 in both oocytes and zygotes. Treatment with 5-azacytidine reverted DNA hypermethylation but did not rescue the developmental arrest of mutant embryos. Taken together, this study demonstrates that PADI6 controls both nuclear and cytoplasmic oocyte processes that are necessary for pre-implantation epigenetic reprogramming and ZGA.
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Overall design |
scRNA-seq and scBS-seq were perfomed on MII oocytes and 2cell embryo from new mutant mouse line carrying human variant of PADI6 gene. We sequenced 44 MII oocytes, 44 2cell embryo and 8 Negative control.
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Contributor(s) |
Giaccari C, Cecere F, Argenziano L, Pagano A, Galvao A, Acampora D, Rossi G, Mele BH, Acurzio B, Coonrod S, Cubellis MV, Cerrato F, Andrews S, Sandra S, Kelsey G, Riccio A |
Citation(s) |
38453481 |
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Submission date |
Oct 15, 2023 |
Last update date |
Apr 17, 2024 |
Contact name |
Francesco Cecere |
E-mail(s) |
francesco.cecerengs@gmail.com
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Phone |
3888903265
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Organization name |
University of Campania "Luigi Vanvitelli"
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Department |
DiStABiF
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Lab |
Riccio
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Street address |
Via A. Vivaldi, n. 43
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City |
Caserta |
State/province |
Caserta |
ZIP/Postal code |
81100 |
Country |
Italy |
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Platforms (1) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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Samples (1) |
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This SubSeries is part of SuperSeries: |
GSE245426 |
A maternal-effect Padi6 variant causes nuclear and cytoplasmic abnormalities in oocytes as well 2 as failure of epigenetic reprogramming and zygotic genome activation in embryos |
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Relations |
BioProject |
PRJNA1028327 |
Supplementary file |
Size |
Download |
File type/resource |
GSE245425_RAW.tar |
6.8 Mb |
(http)(custom) |
TAR (of VCF) |
SRA Run Selector |
Raw data are available in SRA |
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