Centre for Regenerative Medicine

PRC1 influences how DNA is packaged in the nucleus during early development

1 June 2020

Dr Rob Illingworth, Group Leader at CRM, and colleagues from the MRC Human Genetics Unit have been studying the role of the PRC1 protein complex in shaping the landscape of the cell nucleus.

PRC1 controls the development of cell identity (what specialised function a cell has). The complex works by reducing the expression of genes by modifying the chemical and physical properties of chromatin (the packaged form of DNA). It is a principal member of the polycomb repressive complexes (PRC) family of essential epigenetic gene repressors. However, how the interactions of PRC1 influence nuclear organisation, and how this determines what gene products are produced (transcription) remains poorly understood.

In this study, the research team explored the relationship between PRC1-mediated gene repression and chromatin packaging in mouse embryonic stem cells grown in a laboratory. They found that a subfamily of PRC1 causes physical clustering of repressed (switched off) genes within the cell nucleus. These interactions control not only the local architecture of chromatin, but also more broadly determines how DNA is packaged within the cell nucleus.

Equivalent gene clustering was also observed in mouse embryonic tissue, with physical contacts between genes being lost upon their activation, showing that this can happen in a live embryo as well as in embryonic stem cells grown in the lab.

The study used a combination of cell imaging and Hi-C analysis, a high throughput analysis of interactions between DNA fragments, to determine which genes co-localise in 3D space.

Cellular diversity is governed by differential gene expression. These findings therefore lead to a greater understanding of how different cell types are produced in mammals.

“This study provides critical insight into the structural functions of this family of essential developmental regulators and the crosstalk between DNA topology and gene expression.”

Dr Rob Illingworth, Group Leader, Centre for Regenerative Medicine

The study is published in the journal Genes and Development and was funded by the Medical Research Council. doi:10.1101/gad.336487.120. 

 

Dr Rob Illingworth Research Group