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Polycomb Chromatin Topology Enables Long-Range Enhancer Recruitment during Craniofacial Development [ChIP-seq]

GSE295340 Mus musculus Genome binding/occupancy profiling by high throughput sequencing 42 samples Submitted 2026/04/08 Platform GPL17021Platform GPL24247
Summary
Little is known about how three-dimensional chromatin topology shapes mammalian craniofacial development. In mouse cranial neural crest cells, a Polycomb Repressive Complex 2 (PRC2)-dependent chromatin architecture is established before migration. This configuration maintains craniofacial gene promoters poised and connects them with distal Polycomb tethering elements, positioning promoters in spatial proximity to future long-range enhancers. Deletion of Ezh2 disrupts this early topology, causing inappropriate gene derepression in post-migratory craniofacial subpopulations where these genes are normally silenced, and failure of long-range enhancer recruitment where activation is required, thereby impairing proper gene expression. We further identify a distal Polycomb tethering element essential for Hoxa2 enhancer recruitment across topologically associating domains. Thus, Polycomb acts not only as a transcriptional repressor, but also as a chromatin-folding organizer that prepares developmental genes for later activation, by facilitating subsequent recruitment of distal active enhancers previously not in contact. Polycomb-mediated topology therefore orchestrates the transition from progenitor plasticity to precise spatiotemporal control of morphogenetic gene programs during neural crest development and face formation.
Published in
Polycomb chromatin topology enables long-range enhancer recruitment during craniofacial development
Ben Zouari Y, Joshi O, Salvi A et al. · Nature communications 2026 · PMID 42135326 · doi:10.1038/s41467-026-73065-5
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Direct links to NCBI, no account and no request form: the whole study as GSE295340_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 42 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1254229 and SRA study SRP580689. Searching any of these in the dataset finder brings you back here.

Study design
39 conditions, each sampled once — no replicated groups
ChipSeq_PA2_E11.5_WT_H3K27ac ×2

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