October 9, 2018

Retention of the regulatory landscape in mitosis

Differential recruitment of proteins to chromatin is fundamental in eukaryotes to regulate transcription, replication, and cell division. Yet it is unclear how the regulatory landscape is transmitted through cell division since many proteins are thought to be evicted during mitosis, when the chromosomes condensate. A recently published study by the Schübeler group suggests that many transcription factors actually remain bound and could serve as ‘bookmark’ throughout mitosis.

In order to interrogate the binding behavior of chromatin proteins during the cell cycle, Paul Ginno from the Schübeler group and collaborators developed a novel mass spectrometry-based approach, namely biophysical separation of formaldehyde cross-linked protein-DNA complexes, to quantify the chromatin-associated proteome at separate stages of the cell cycle. Critical to the success of this project was the close collaboration with the Proteomics and Protein Analysis Facility, headed by Jan Seebacher.

The study, which was published in Nature Communications last week, suggests that mitotic retention of transcription factors is more widespread than previously appreciated. The authors speculate that this persistent binding serves to reinitiate transcriptional programs more readily post mitosis. Nevertheless, retention is pathway specific as proteins involved in the process of transcription itself, or epigenetic modifiers associated with transcriptional activity, show reduced binding to mitotic chromatin.

"This study is valuable in various aspects," says Dirk Schübeler, the group leader of the lab where Ginno conducted these postdoctoral studies. "First, Paul developed a robust method to study chromatin-bound proteins that can be applied to many questions; this is an important achievement given the inherent difficulties for the quantitative analysis of chromatin. Second, the study provides a comprehensive catalog of chromatin changes during the cell cycle. Third – and most interestingly – Paul could show that a high percentage of proteins and epigenetic modifiers stay on chromatin throughout the cell cycle; this is quite some news!"

Original publication:
Paul Adrian Ginno, Lukas Burger, Jan Seebacher, Vytautas Iesmantavicius, Dirk Schübeler (2018) Cell cycle-resolved chromatin proteomics reveals the extent of mitotic preservation of the genomic regulatory landscape. Nature Communications 9:4048.

FMI Mitotic chromosome: most transcription factors bind mitotic chromatin to varying degrees. Retention of epigenetic modifiers is more pathway specific; while proteins associated with transcription are often evicted (ex. Histone acetyltransferases, HATs), those associated with transcriptional repression remain bound (ex. Histone deacetylases, HDACs).