ArticleNature structural & molecular biology2024
Lineage regulators TFAP2C and NR5A2 function as bipotency activators in totipotent embryos.
Article in Nature structural & molecular biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 40 citations in OpenAlex.
- TRIM37 interacts with TRIM28 to maintain primordial germ cell identity during migration.Cell research · 2026Article
- Decoding stage-specific functions of PRC2 in early embryogenesis uncovers roles in preimplantation development and primordial germ cell fate.Nature cell biology · 2026Article
- Mechanisms coordinating exit from the stem cell state in mammals.Genes & development · 2026Review
- Multi-omics and low-input proteomics profiling reveals dynamic regulation driving pluripotency initiation in early mouse embryos.FEBS open bio · 2026Article
- TFAP2C protects against ferroptosis in ovarian cancer through the KEAP1-NRF2 axis by recruiting HDAC1/2.Oncogene · 2026Article
- Nascent transcriptome of embryonic genome activation reveals a regulatory axis linking transcriptional priming to early lineage specification in mouse embryos.Nucleic acids research · 2026Article
- Depletion of Sorcs3 Activates Totipotency in Mouse Embryonic Stem Cells by Modulating Key Signaling Pathways.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- TPST2-mediated tyrosine sulfation orchestrates porcine preimplantation development.BMC biology · 2026Article
- Decoding the cell intrinsic and extrinsic roles of PRC2 in early embryogenesis.bioRxiv : the preprint server for biology · 2026Article
- Distal enhancers regulate mammalian early embryonic lineage differentiation through long-range interactions.Nucleic acids research · 2026Article
- Feed-forward loops by NR5A2 ensure robust gene activation during pre-implantation development.Development (Cambridge, England) · 2026Article
- Role of CEBPa in trophectoderm competence installment.Science advances · 2025Article
- Epigenetic regulation of NR5A2 influences colorectal cancer cell stemness via a stemness-related transcription factor NANOG.Cell communication and signaling : CCS · 2025Article
- Maternal factor OTX2 regulates human embryonic genome activation and early development.Nature genetics · 2025Article
- A continuous totipotent-like cell-based embryo model recapitulates mouse embryogenesis from zygotic genome activation to gastrulation.Nature cell biology · 2025Article
- Remodelling bivalent chromatin is essential for mouse peri-implantation embryogenesis.Nature cell biology · 2025Article
- Article
- Regulation of autophagy and its role in late preimplantation during mouse embryo development.Scientific reports · 2025Article
- Deciphering the role of cis-regulatory elements and TFAP2C in the activation of zygotic Sox2 expression in mouse preimplantation embryos.Development (Cambridge, England) · 2025Article
- A long noncoding RNA with enhancer-like function in pig zygotic genome activation.Journal of molecular cell biology · 2025Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During the first lineage segregation, a mammalian totipotent embryo differentiates into the inner cell mass (ICM) and trophectoderm (TE). However, how transcription factors (TFs) regulate this earliest cell-fate decision in vivo remains elusive, with their regulomes primarily inferred from cultured cells. Here, we investigated the TF regulomes during the first lineage specification in early mouse embryos, spanning the pre-initiation, initiation, commitment, and maintenance phases. Unexpectedly, we found that TFAP2C, a trophoblast regulator, bound and activated both early TE and inner cell mass (ICM) genes at the totipotent (two- to eight-cell) stages ('bipotency activation'). Tfap2c deficiency caused downregulation of early ICM genes, including Nanog, Nr5a2, and Tdgf1, and early TE genes, including Tfeb and Itgb5, in eight-cell embryos. Transcription defects in both ICM and TE lineages were also found in blastocysts, accompanied by increased apoptosis and reduced cell numbers in ICMs. Upon trophoblast commitment, TFAP2C left early ICM genes but acquired binding to late TE genes in blastocysts, where it co-bound with CDX2, and later to extra-embryonic ectoderm (ExE) genes, where it cooperatively co-occupied with the former ICM regulator SOX2. Finally, 'bipotency activation' in totipotent embryos also applied to a pluripotency regulator NR5A2, which similarly bound and activated both ICM and TE lineage genes at the eight-cell stage. These data reveal a unique transcription circuity of totipotency underpinned by highly adaptable lineage regulators.
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