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Hyper transcription underlines de novo establishment of 3D chromatin architecture in mouse early embryos

ABSTRACT: After fertilization, early embryos undergo dissolution of conventional chromatin organization including topologically associating domains (TADs)1,2. Zygotic genome activation (ZGA) then commences amid unusually slow de novo establishment of 3D chromatin architecture2. How chromatin organization is established and how it interplays with transcription in early mammalian embryos remain elusive. Here, we show that CTCF occupies chromatin throughout mouse early development. By contrast, cohesin poorly binds chromatin in 1-cell embryos, coinciding with TAD dissolution. Cohesin binding then progressively increases from 2-cell to 8-cell embryos, accompanying TAD establishment. Unexpectedly, strong “genic cohesin islands (GCIs)” emerge across gene bodies of active genes in this period. GCI genes enrich for cell identity and regulatory genes, exhibit broad H3K4me3 at promoters, and display strong binding of transcription factors and the cohesin loader NIPBL at nearby enhancers. We show that transcription is hyperactive in 2-8-cell embryos and is required for GCI formation. Conversely, induced transcription can also create GCIs. Finally, GCIs can function as insulation boundaries and form contact domains with nearby CTCF sites, promoting both the transcription levels and stability of GCI genes. These data reveal a hypertranscription state in early embryos that both shapes and is fostered by the 3D genome organization, revealing intimate interplay between chromatin structure and transcription.

ORGANISM(S): Mus musculus

PROVIDER: GSE200323 | GEO | 2025/06/11

REPOSITORIES: GEO

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