Chromatin protein profiling during the mammalian cell cycle reveals the extent of mitotic preservation of the regulatory landscape

ABSTRACT: While regulation of transcription, replication and cell division relies on dynamic protein binding to DNA and chromatin, it is unclear which regulatory components remain bound to compacted mitotic chromosomes. To comprehensively quantify the chromatin-associated proteome in different phases of the cell cycle, we utilized the buoyant density of DNA-protein complexes after crosslinking. This revealed variable associations for thousands of proteins to DNA including their frequent and variable phosphorylation. While epigenetic modifiers that promote transcription are lost from mitotic chromatin, repressive modifiers generally remain associated. Interestingly, 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 genome-wide measurements of chromatin accessibility confirm. This work establishes a novel approach to study chromatin, provides a comprehensive catalogue of chromatin changes during the cell cycle, and reveals the degree with which the genomic regulatory landscape is maintained through mitosis.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cerebral Cortex Glial Cell, Cell Culture

DISEASE(S): Brain Glioblastoma Multiforme

SUBMITTER: Paul Ginno  

LAB HEAD: Dirk Schübeler

PROVIDER: PXD008033 | Pride | 2018-09-06

REPOSITORIES: pride