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bioRxiv · 10.1101/2024.05.09.593364

T-ChIC: multi-omic detection of histone modifications and full-length transcriptomes in the same single cell

Zeller, P.·Blotenburg, M.·Bhardwaj, V.·de Barbanson, B. A.·Salmen, F.·van Oudenaarden, A.
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Abstract

Epigenetic mechanisms, including histone modifications, are key regulators of transcription and influence cellular differentiation. To uncover the interplay between histone modifications and transcription, we developed T-ChIC (Transcriptome + Chromatin ImmunoCleavage), which detects full-length transcripts and histone modifications in the same single cell. We applied T-ChIC to gastruloids, an in vitro model containing cell types derived from all three germ layers. During gastruloid development we observed a switch in transcription start site usage from multiple regions marked by H3K4me3 to one marked start site per gene. H3K27me3 coverage transitions from global marking of non-transcribed regions towards localised marking of repressive regions. Upon lineage commitment, bivalent regions are sequentially resolved towards a germ layer-specific state, where endoderm retains a high abundance of H3K27me3 while ectoderm displays a widespread loss. Together, we propose a model for a cell-intrinsic epigenetic timer, which ensures sequential perceptiveness of pluripotent cells to transcriptional activation of germ layer-specific genes.

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Zeller, P., Blotenburg, M., Bhardwaj, V., de Barbanson, B. A., Salmen, F., van Oudenaarden, A.. 2024-05-13. T-ChIC: multi-omic detection of histone modifications and full-length transcriptomes in the same single cell. https://doi.org/10.1101/2024.05.09.593364

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