Life & Chemistry

Dynamic DNA Packaging: New Insights into Gene Regulation

Discovery could help scientists to understand how cells ’remember’ which genes to switch on or off

Scientists from Imperial College London, the Medical Research Council, Cancer Research UK and the Hammersmith Hospital have discovered an important aspect of how heterochromatin, the wrapping around DNA, works.

The researchers, whose work is published today in Science, discovered that heterochromatin is dynamic, constantly wrapping and unwrapping around DNA, and not static as previously thought. This packaging is one way in which the cell limits which genes are turned on, ’locking-in’ different patterns of gene expression in different cell types.

Dr Richard Festenstein from Imperial College London and the MRC Clinical Sciences Centre, at the Hammersmith Hospital comments: “Although this research improves our basic understanding of how cells ’remember’ which genes to ’switch on or off’, it could also help us understand diseases which are linked to inappropriate ‘switching’, such as cancer, and several inherited diseases.”

Previously heterochromatin was thought to be a static structure, which stabilised crucial aspects of nuclear organisation and prohibited access to transcription factors. Heterochromatin protein 1 (HP1b) is a key component of condensed DNA, and is strongly implicated in gene silencing.

The researchers tagged HP1b with a green fluorescent protein to allow them to follow its movement, and discovered that HP1b moves rapidly within and between the euchromatin (loosely packaged DNA) and heterochromatin (densely packaged DNA) of mouse immune cells.

Dr Festenstein adds: “The previous view that heterochromatin was a sort of static ‘molecular-glue’ has been shattered, revealing a dynamic way of regulating access of crucial factors to DNA.

“There are many protein factors which need to get to the DNA, such as DNA repair factors, factors which switch on genes and factors required for DNA replication when each cell divides. We also discovered that immune cell activation greatly increased this HP1b mobility, indicating that such a process may facilitate the remodelling of heterochromatin and thereby regulate the access these key factors to the DNA. ”

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