4.8 Article

Independence of chromatin conformation and gene regulation during Drosophila dorsoventral patterning

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NATURE GENETICS
卷 53, 期 4, 页码 487-+

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NATURE PORTFOLIO
DOI: 10.1038/s41588-021-00799-x

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  1. Max Planck Society
  2. Deutsche Forschungsgemeinschaft (DFG) Priority Programme SPP2202 `Spatial Genome Architecture in Development and Disease' [422857230]
  3. DFG Clinical Research Unit CRU326 `Male Germ Cells: from Genes to Function' [329621271]
  4. European Union [643062]
  5. Medical Research Council, UK [MC UP 1605/10]
  6. Academy of Medical Sciences
  7. Department of Business, Energy and Industrial Strategy [APR3\1017]
  8. Alexander von Humboldt-Stiftung
  9. Swedish Research Council (Vetenskapsradet)
  10. Swedish Cancer Society (Cancerfonden)
  11. NIH [GM118147]
  12. Marie Curie Actions (MSCA) [643062] Funding Source: Marie Curie Actions (MSCA)

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Chromatin organization is largely independent of dorsoventral gene expression in early Drosophila embryonic development, with tissue-specific chromatin states and gene expression being maintained across tissues. Tissue-specific chromatin conformation is not necessary for tissue-specific gene expression, but rather acts as a scaffold facilitating gene expression when enhancers become active.
Chromatin conformation is largely independent of dorsoventral gene expression during early embryonic development in Drosophila. Despite tissue-specific differences in chromatin state and gene expression, three-dimensional chromatin organization is maintained across tissues. The relationship between chromatin organization and gene regulation remains unclear. While disruption of chromatin domains and domain boundaries can lead to misexpression of developmental genes, acute depletion of regulators of genome organization has a relatively small effect on gene expression. It is therefore uncertain whether gene expression and chromatin state drive chromatin organization or whether changes in chromatin organization facilitate cell-type-specific activation of gene expression. Here, using the dorsoventral patterning of the Drosophila melanogaster embryo as a model system, we provide evidence for the independence of chromatin organization and dorsoventral gene expression. We define tissue-specific enhancers and link them to expression patterns using single-cell RNA-seq. Surprisingly, despite tissue-specific chromatin states and gene expression, chromatin organization is largely maintained across tissues. Our results indicate that tissue-specific chromatin conformation is not necessary for tissue-specific gene expression but rather acts as a scaffold facilitating gene expression when enhancers become active.

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