Max Planck Institute for Molecular Biomedicine, Münster, Germany.
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
Nat Genet. 2021 Apr;53(4):487-499. doi: 10.1038/s41588-021-00799-x. Epub 2021 Apr 1.
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.
染色质组织与基因调控之间的关系尚不清楚。虽然染色质域和域边界的破坏会导致发育基因的错误表达,但基因组组织调节剂的急性耗竭对基因表达的影响相对较小。因此,尚不确定是基因表达和染色质状态驱动染色质组织,还是染色质组织的变化促进了细胞类型特异性基因表达的激活。在这里,我们使用黑腹果蝇胚胎的背腹模式形成作为模型系统,提供了染色质组织和背腹基因表达独立性的证据。我们定义了组织特异性增强子,并使用单细胞 RNA-seq 将它们与表达模式联系起来。令人惊讶的是,尽管染色质状态和基因表达具有组织特异性,但染色质组织在很大程度上在组织间保持不变。我们的结果表明,组织特异性染色质构象对于组织特异性基因表达不是必需的,而是在增强子变得活跃时作为促进基因表达的支架发挥作用。