Histone post-translational modification

Posted by MeganBowie on February 1st, 2021

Histone plays an important role not only in chromosome assembly, but also in regulating gene expression. Histone post-translational modifications mostly occur in the N-terminal tail of histone, including methylation, acetylation, phosphorylation, ADP ribosylation, ubiquitination and small molecule ubiquitination. These modifications contribute to the binding of other proteins to DNA, resulting in synergistic or antagonistic effects to regulate gene transcription. For example, acetylation reduces the positive charge of histone tail, which weakens the interaction with negatively charged DNA skeleton and promotes chromatin to be open; methylation activation or inhibition of gene function mainly depends on the site of modification, which is mainly related to the single methylation, double methylation or trimethylation of lysine residues. Histones in eukaryotic cells regulate gene function through various post-translational modifications and their different combinations in time and space. Therefore, post-translational modification of histones is a complex system. As far as native nucleosomes and recombinant nucleosomes are concerned, their N-terminal tail is susceptible to various modifications. For example, in the tail of histone H4, there may be more than 3 million different combinations of modifications. In order to interpret the histone code, it is necessary to identify all possible histone modifications and the relationship between specific modification sites or modification patterns and specific biological functions, such as transcription, replication, chromosome condensation, gene silencing or apoptosis.

The traditional method of histone post-translational modification is to integrate radioactive precursor molecules and then hydrolyze histone completely to analyze amino acid residues. This method requires a large amount of samples, involves radioactive reagents, and can not always obtain accurate modification map. In early studies, histone acetylation, methylation and phosphorylation were identified by this method.

Following the traditional histone modification analysis technology, the acetylation specific antibody of histone H4 was developed in the late 1980s. Using this antibody and Western blot hybridization technology, not only the acetylation sites of histone H4 were identified, but also different modification sites were distinguished. And with the application of fluorescence technology in antibody technology, we can locate specific histone modification sites in specific regions of the genome at the first time. With the development of antibody technology, it has been widely used in other post-translational modifications of histones, such as methylation of lysine and arginine or phosphorylation of serine and threonine.

Mass spectrometry is a physical and chemical analysis technology, which can determine the mass charge ratio of gasification ions. Mass spectrometry is the core strategy of proteomics research. It can analyze all kinds of protein modifications without bias and at the same time. It can also analyze the differences of protein expression and modified proteins. Mass spectrometry has been successfully applied to histone analysis and has become an important tool for histone translation modification.

Conclusion and Prospect

Histone post-translational modification is a challenging research field. With the improvement of methodology and the emergence of new technologies, it will be helpful to promote the research of histone. The application of mass spectrometry technology provides a new insight for the study of chromatin biology. It can not only identify new histone modifications and their sites, quantitative histone modifications and combinatorial histone modifications, but also provide a powerful tool for interpreting histone codes.

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Creative BioMart can offer a variety of native and recombinant nucleosomes. Whether it is with or without post-translational modifications (PTMs), or with histone variants, or with methylated DNA, you can find it here.