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. 2025 Nov 12;5(11):101002.
doi: 10.1016/j.xgen.2025.101002. Epub 2025 Sep 15.

3D chromatin structures precede genome activation in Drosophila embryogenesis

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Free article

3D chromatin structures precede genome activation in Drosophila embryogenesis

Gabriel A Dolsten et al. Cell Genom. .
Free article

Abstract

3D chromatin structure is critical for the regulation of gene expression during development. Here we used Micro-C assays at 100-bp resolution to map genome organization in Drosophila melanogaster throughout the first half of embryogenesis. These high-resolution contact maps reveal fine-scale features such as loops and boundaries delineating topologically associating domains. Notably, we observe that 3D chromatin structures form prior to zygotic genome activation and persist during successive mitotic cycles. Integrative analysis with 149 public chromatin immunoprecipitation sequencing (ChIP-seq) datasets identifies four classes of chromatin structuring elements, including a distinct group enriched for GAGA-associated factor (GAF) and Zelda binding, associated with developmental-gene regulation. These elements are mitotically retained and exhibit sequence and structure similarity between D. melanogaster and D. virilis. We propose that 3D chromatin organization in the pre-cellular embryo facilitates deployment of developmentally regulated genes during Drosophila embryogenesis.

Keywords: ChIP-seq; Drosophila; Micro-C; TAD; chromatin boundaries; chromatin loops; clustering; computation; development; embryo; insulators; nucleosome.

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Conflict of interest statement

Declaration of interests E.M.C. is currently an employee at Asimov. X.Y.B. is currently an employee at BlueRock Therapeutics.

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