Seeing the Bigger Picture – Spatially Resolving Chromatin Modification Profiles with Spatial-CUT&Tag

Seeing the Bigger Picture – Spatially Resolving Chromatin Modification Profiles with Spatial-CUT&Tag

Demonstrating the Potential of Spatial-CUT&Tag in Mouse Embryos

In this study, the authors assayed histone modifications associated with repressed loci , activated promoters , and activated enhancers and/or promoters employing highly-specific antibodies. Initially, they discovered that different spatial-CUT&Tag experiments in early mouse embryos displayed reproducibility (chromatin modification state pattern and peaks) with data agreeing with chromatin immuno precipitation-sequencing experiments. Mapping histone modification clusters to specific locations helped to detect spatially distinct patterns that agreed with tissue histology in adjacent tissue sections, suggesting that chromatin modification states can identify cell types in the mouse embryo. Indeed, the authors demonstrated that spatial-CUT&Tag could distinguish major cell types in early mouse embryos, while examining cell-type-specific marker gene expression (associating H3K27me3 with repressed genes and H3K4me3 and H3K27ac with active genes) proved the utility of spatial-CUT&Tag to detect spatial patterning during development. Correlating gene expression from single-cell RNA-sequencing and H3K27ac at candidate enhancers also successfully predicted experimentally validated enhancer-gene interactions.

 

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