The Drosophila ZAD zinc finger protein Mulberry shapes the organization of the regulatory genome in the early embryo

Umemura, Y.; Fukaya, T.

doi:10.64898/2026.02.03.703437

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bioRxiv · 10.64898/2026.02.03.703437

The Drosophila ZAD zinc finger protein Mulberry shapes the organization of the regulatory genome in the early embryo

Umemura, Y.·Fukaya, T.

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Abstract

Long-range regulatory interactions play a fundamentally important role in the control of gene activity during animal development, yet the underlying mechanisms remain largely unclear. Here, we identified a zinc finger-associated domain (ZAD)-C2H2 zinc finger protein, CG31365/Mulberry, as a looping factor that mediates long-range tethering activity in the early Drosophila embryo. Evidence is provided that Mulberry is specifically recruited to a subset of loop anchors and topological boundaries at key developmental loci to shape genome organization and gene activity. Super-resolution imaging analysis revealed that Mulberry forms nuclear condensates that associate with its target loci through the structured N-terminal ZAD domain. Micro-C analysis further demonstrated that the formation of loops and boundaries is lost in the condensation-deficient Mulberry mutant in a locus-specific manner. We propose that Mulberry acts as a condensation-dependent structural regulator of genome topology, organizing "multi-way regulatory hubs" that mediate long-range gene activation during early embryogenesis.

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Umemura, Y., Fukaya, T.. 2026-02-05. The Drosophila ZAD zinc finger protein Mulberry shapes the organization of the regulatory genome in the early embryo. https://doi.org/10.64898/2026.02.03.703437

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