Histones hit the mark
Section of mouse testis tubules, location of sperm development.
During their maturation, spermatogenic cells move towards the tubule lumen. Importantly nucleosomes are destabilized in elongating spermatids (near the lumen) and replaced by other proteins allowing full condensation of the nucleus. The brown staining in the figure clearly reveals a high enrichment of H3K64Ac at this moment of sperm development.
March 25, 2014
The study of histones and their modifications is essential for the comprehension of gene expression. The group of Robert Schneider from the IGBMC discovered that one of these specific modifications, an acetylation, plays a role in the interaction histones/DNA. These results, published in the journal eLife, stress an implication of this histone mark in genome reorganization during the mouse sperm development and regulation of gene expression.
Gene expression is a quite complex process. Thinking that the well-known DNA is self-sufficient is a mistake. DNA is not free in the cell nucleus but wrapped around specific proteins called histones, like a thread around a spool. Histones and DNA are packed together into chromatin, whose level of compaction allows the cell to regulate gene expression.
Histones are composed of a globular domain and a flexible tail that protrudes from the nucleosome. They carry specific small chemical modifications which have impacts on gene expression. Acetylation fosters for instance gene expression by giving chromatin an open configuration. Histone tail-modifications were intensively studied in the last decade but not the ones present within the globular part of the histones. The group of Robert Schneider is interested in these latter modifications which are located in close contact to the wrapped DNA.
Under Sylvain Daujat’s direction and in collaboration with other research groups, Vincenzo Di Cerbo showed in a recent publication that one of these specific modifications, the acetylation of the lysine 64 on histone H3 (H3K64Ac) plays an important role in the regulation of nucleosome stability. Indeed, they observed a reduction in the interaction between DNA and histones in the presence of this acetylation. Dr. Schneider explains that “stability decrease of the nucleosome leads to the stimulation of gene expression, by making the first step of this process easier”.
To go further, they also checked the presence of this modification during mouse sperm development. This step sees sperm chromatin going through an important reorganization: there is a global nucleosome disassembly in order that histones are replaced by other proteins. Interestingly, right within this period, H3K64Ac is found highly enriched in the sperm chromatin, strengthening its potential role in the destabilisation of the nucleosome.
This study also emphasizes the idea of a balance between repressive or permissive histone marks. The authors only observe the presence of H3K64Ac when its repressive counterpart H3K64me3 (the methylated form of H3K64) is absent and vice versa. The acetylation and methylation of the same position within histone H3 can therefore define active or repressive chromatin.
Knowing that histone modifications are altered in cancer, the discovery of this new histone mark could make a breakthrough in the understanding of the mechanisms leading to cancer.