Dataset Information

Ftdc1/2, maternal-effect genes required for methylation maintenance and embryonic development

ABSTRACT: The oocyte serves the different purpose of transmitting the maternal genome and factors that are critical for post-fertilization events. Through the screening of oocyte-specific factors, here we identify two hitherto uncharacterized murine genes, ferritin domain containing 1 and 2 (Ftdc1 and Ftdc2), as novel maternal-effect genes. Genetic ablation of Ftdc1 or Ftdc2 causes postimplantation defects and female infertility, despite having little impact on oogenesis and preimplantation development. Nevertheless, post-transcriptional events in these mutant oocytes are disrupted. Importantly, FTDC1 or FTDC2 depletion induces the progressive loss of genomic methylation in early embryos. This loss correlates with a marked reduction in oocyte-specific DNA methyltransferase 1 (DNMT1o) protein, due to its increased degradation via the ubiquitin-proteasome pathway. Mechanistically, we reveal that FTDC1, FTDC2 and DNMT1o form a complex by direct interactions, thereby stabilizing each other. Moreover, comparison with DNA and histone methylation profiles in Dnmt1-null embryos indicates the functional uniqueness of FTDC1/2. These findings demonstrate that maternal FTDC1 and FTDC2 are crucial players in maintaining DNA methylation during embryogenesis and determining female fertility, offering new insights into the epigenetic control of mammalian development.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Egg, Oocyte

SUBMITTER: Yueshuai Guo

LAB HEAD: Xuejiang Guo

PROVIDER: PXD045608 | Pride | 2025-10-29

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	MouseEgg_Ftdc2_TMT6_HPRP_frc10_20200611.raw	Raw
	MouseEgg_Ftdc2_TMT6_HPRP_frc11_20200611.raw	Raw
	MouseEgg_Ftdc2_TMT6_HPRP_frc12_20200611.raw	Raw
	MouseEgg_Ftdc2_TMT6_HPRP_frc13_20200611.raw	Raw
	MouseEgg_Ftdc2_TMT6_HPRP_frc14_20200611.raw	Raw

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Publications

FTDC1/2, oocyte-specific cofactors of DNMT1 required for epigenetic regulation and embryonic development.

Li Congyang C Li Jiashuo J Du Siyu S Ma Yunfei Y Guo Yueshuai Y Zhang Xiangzheng X Wang Bing B Zhu Shuai S An Huiqing H Chen Ming M Guo Junjie J Han Longsen L Ge Juan J Qian Xu X Schedl Tim T Guo Xuejiang X Wang Qiang Q

Cell death and differentiation 20250428 11

The unique epigenetic patterns during gametogenesis and embryonic development indicate the existence of specialized methylation machinery. In the present study, we describe the discovery of two oocyte-specific cofactors of DNA methyltransferase 1 (DNMT1), encoded by uncharacterized genes, ferritin domain containing 1 and 2 (Ftdc1 and Ftdc2). Genetic ablation of Ftdc1 or Ftdc2 causes midgestation defects and female infertility. FTDC1 or FTDC2 depletion induces the progressive loss of DNA methylat ...[more]

PMID: 40295817

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Project description:There are two major developmental transitions that take place during the first four days of mouse embryogenesis. The first one is the maternal-to-zygotic transition in the zygote and 2-cell embryo, the second one is the first cell lineage commitment at the 32-cell stage. A number of transcription factors govern zygotic expression and the specification of pluripotent versus trophectoderm cells, while at the same time there are dynamic changes in DNA methylation and chromatin organization. It is not fully understood which chromatin modifying complexes take part in these processes and whether there is a particular spatiotemporal distribution of certain chromatin players in preimplantation development. To address this question, we performed gene expression profiling of single cells from the oocyte to the blastocyst stage. We describe the patterns of expression of over 100 genes involved in histone methylation, DNA methylation and chromatin remodelling. For a number of these genes we observed differential maternal versus zygotic expression. This is particularly the case for homologous genes like Tet1 and Tet3 (zygotic and maternal respectively), or Suv39h1 and Suv39h2 (zygotic and maternal respectively). In contrast to the maternal-to-zygotic switch, most chromatin modifying genes are ubiquitously expressed in the subsequent lineage specification at the 32-cell stage. The few exceptions that showed a differential expression pattern are Kdm1b, Tet1 and Prdm14. Our data suggests that genes coding for histone modifying complexes are ubiquitously expressed in early embryos and that there are maternal and zygotic variants of most of these complexes. Furthermore, the method that we applied, allows the distinction of female versus male embryos based on the expression of Xist (X-linked, expressed in female embryos) and Kdm5d (Y-linked, expressed strongly in male embryo). With the exception of the X- and Y-linked genes, we did not observe sex-specific gene expression patterns of chromatin modifiers or transcription factors.