Cell cycle-resolved chromatin proteomics reveals the extent of mitotic preservation of the genomic regulatory landscape

Paul Adrian Ginno, Lukas Burger, Jan Seebacher, Vytautas Iesmantavicius and Dirk Schübeler ()
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Paul Adrian Ginno: Friedrich Miescher Institute for Biomedical Research
Lukas Burger: Friedrich Miescher Institute for Biomedical Research
Jan Seebacher: Friedrich Miescher Institute for Biomedical Research
Vytautas Iesmantavicius: Friedrich Miescher Institute for Biomedical Research
Dirk Schübeler: Friedrich Miescher Institute for Biomedical Research

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: Abstract Regulation of transcription, replication, and cell division relies on differential protein binding to DNA and chromatin, yet it is unclear which regulatory components remain bound to compacted mitotic chromosomes. By utilizing the buoyant density of DNA–protein complexes after cross-linking, we here develop a mass spectrometry-based approach to quantify the chromatin-associated proteome at separate stages of the cell cycle. While epigenetic modifiers that promote transcription are lost from mitotic chromatin, repressive modifiers generally remain associated. Furthermore, while proteins involved in transcriptional elongation are evicted, most identified transcription factors are retained on mitotic chromatin to varying degrees, including core promoter binding proteins. This predicts conservation of the regulatory landscape on mitotic chromosomes, which we confirm by genome-wide measurements of chromatin accessibility. In summary, this work establishes an approach to study chromatin, provides a comprehensive catalog of chromatin changes during the cell cycle, and reveals the degree to which the genomic regulatory landscape is maintained through mitosis.

Date: 2018
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DOI: 10.1038/s41467-018-06007-5

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