2017 February 1

IJC Researcher co-authors an important review paper

Marcus Buschbeck and Sandra Hake have published an article on the state of the art in histone biology in Nature Reviews Molecular Cell Biology.

Marcus Buschbeck of the Chromatin, Metabolism and Cell Fate Group at the IJC, has co-authored a prestigious review paper that outlines the current knowledge of histones; a protein family involved in the packaging of DNA within the nuclei of cells. Dr Buschbeck's group has made many contributions to the study of histones and the publication of this review in a high impact journal will provide greater visibility for the group and the institute.

DNA is not loose in cells as long chains, but tightly wound around proteins like beads on a necklace to form the familiar chromosome shape; the whole DNA and protein structure is called chromatin. By opening and closing the coils and changing shape the chromatin plays a key role in regulating which genes are active and which are not at any given moment.

The histones are essential elements within the chromatin structure. There are 4 core histones, which are deposited onto the DNA when it replicates and produces a new strand; these histones are encoded by groups of genes that tend to be clustered together on the genome. However, there are many variations of the first three histones; these appear in many different but very specific places along the genome and endow it with specific properties. Complex cellular machineries, involving other proteins, control the deposit onto and removal of the histone variants from the genome. The variants are deposited on the DNA throughout the cell cycle and not just during DNA replication and they tend to be coded for by single genes, which are not usually found in the clusters. In summary, each histone variant appears at a unique time during the life cycle of the cell and the review discusses how their presence affects the functioning of the whole cell.

The many histone variants are involved in very different cellular processes. Some are important for early embryo development and regulate which types of cells stem cells develop into, also the reverse when regular cells return to a "stem-like" state and begin to divide again. Recent research has also increased our knowledge on how mutations, changes in protein production and the machineries for depositing histone variants could be involved in tumor development.

Until now this particular part of the structure of cells has not been explored to see whether they can serve as markers for disease progression to be used as diagnostic or prognostic tools or even as targets for new drugs to stop the development of disease. The authors stress the importance of understanding the complex biology of histone variants better as they could well provide new targets for personalized medicine.

Nat Rev Mol Cell Biol. 2017 Feb 1. doi: 10.1038/nrm.2016.166. [Epub ahead of print] Variants of core histones and their roles in cell fate decisions, development and cancer.
Buschbeck M1,2, Hake SB3,4.