How a histone ‘switch’ regulates chromatin dynamics

The modification of the phosphorylation of the serine 31 (SER31) (H3.3S31PH) in the n-terminal tail of the histone H3.3 variant can transform nucleosomes H3.3 of a stable state into a dynamically activated configuration, providing new information in the mechanisms of epigenetic regulation. However, the specific mechanisms by which H3.3 influences the stability and dynamics of nucleosomes remain vague.

In a new study published in Nucleic acid search On September 12, a research team led by Professor Li Wei of the Biophysics Institute of the Chinese Academy of Sciences, as well as Professor Chen of the Medical University of the capital of the capital, for the first time, discovered how H3.3 and its phosphorylation Ser31 regulated the responses of the dynamics of nucleosomes and transcription.

Using a combination of in vitro experiences of a single molecule and analyzes at the genome scale, researchers have shown that although the incorporation of H3.3 does not significantly modify the mechanical stability of nucleosomes, it considerably improves their ability to maintain integrity after disturbance.

A key discovery was that H3.3 recruits the fact of facts (facilitates the transcription of chromatin) more effectively than canonical H3. The fact generally destabilizes nucleosomes, but when linked to nucleosomes containing H3.3, it rather promotes a stable state oriented towards maintenance.

The researchers also identified the phosphorylation of H3.3 to SER31 as a critical molecular switch which reverses this stability. H3.3S31PH transforms nucleosome from a stable state into a dynamic and active configuration which facilitates rapid transcriptional activation. This modification is specifically induced in macrophages during stimulation, where it dynamically modulates the affair of the facts, the nucleosomes and the ensuing transcriptional response.

These results provide new mechanistic information on how the interaction between a histone variant, its post-transduction modification and a histone chaperone complex can precisely regulate the chromatin dynamics.

The study underlines the importance of H3.3S31PH as a pivot regulator to allow a rapid passage of the transcriptional plate to activation in immune responses. He also suggests potential therapeutic implications in the treatment of diseases involving deregulation of chromatin, such as inflammatory disorders and cancer.