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Chromosomes fold into distinct domains that regulate transcription, replication and repair. In addition to well-characterized topologically associating domains (TADs) and compartments, the diversity of heterochromatin domains remains poorly defined at the sequence level.
Using single-molecule tracing of nascent heterochromatin in Caenorhabditis elegans, the study identifies three classes of megabase-scale domains: sharp-boundary, condensin I-dependent TAD-like domains; similarly sized condensin-independent domains; and decompacted diffuse structures that are abundant but likely missed by crosslinking-based assays.
The results uncover previously unrecognized heterochromatin architectures and suggest that maternal transcriptional activity helps shape domain boundaries in early embryos.
Pulido-Barrera, D. C., You, J. E., Angonezi, A. L., Kuznetsov, A., Xu, F., Verheijen, T., Saw, A. N., Kos, P., Giorgetti, L., Molina, N., Brückner, D., & Mango, S. E. (2026). Single-molecule chromatin tracing reveals a diversity of megabase heterochromatin domains. Nature Structural & Molecular Biology.