ArticleNucleic acids research2026
Distal enhancers regulate mammalian early embryonic lineage differentiation through long-range interactions.
Article in Nucleic acids research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
2 citing papers in PubMed.
- Genome-wide profiling of histone modifications and transcription factor binding at single-cell resolution by DeChIC-seq.Cell research · 2026Article
- YY1 in hematopoietic stem cells: epigenetic regulation, chromatin architecture, and aging.Current opinion in hematology · 2026Review
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Authors and funding
15 authors.
Funding
Abstract
Histone modifications are key regulators of cell lineage differentiation; however, the roles of histone H3 lysine 27 acetylation (H3K27ac) and high-order chromatin structure in the trophectoderm (TE) and inner cell mass (ICM) remain unclear. Using ultra-low-input multi-omics, we profiled H3K27ac, chromatin accessibility, and the transcriptome in both the TE and ICM. Lineage-specific H3K27ac was predominantly enriched at distal enhancers rather than promoters, indicating that first-lineage differentiation relies on distal enhancer activity. Integration with chromatin accessibility data identified key transcription factors cooperating with H3K27ac during peri-implantation. Analysis of high-order chromatin structure revealed lineage-specific enhancer-promoter loops. Further, we identified and functionally validated BRD4, p300, and YY1 at these enhancers, demonstrating their essential roles in morula-to-blastocyst transition. Notably, CBP/p300 inhibition selectively disrupted distal H3K27ac-marked enhancers with minimal effects on promoters, leading to down-regulation of placenta-related genes. Despite similar accessibility and transcription factor binding between the TE and ICM, enhancer activity requires H3K27ac acquisition rather than accessibility alone. These results indicate that H3K27ac-marked distal enhancers regulate early lineage differentiation by promoting lineage-specific gene expression through long-range chromatin interactions. Cross-species comparisons between mice and humans further revealed stronger H3K27ac conservation in the TE than in the ICM of mammalian embryos, highlighting the conserved regulatory role of TE-specific enhancers during early development.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.