Rabbit Anti-Human Histone H3 (Citrullinated R2 / R8 / R17) polyclonal antibody

Histones are the main proteins of chromatin, and one of many covalent post-translational changes they undergo is acetylation, methylation, phosphorylation and so on. These modifications are generally catalyzed by specific modifying and demodifying enzymes. By reversibly modifying histones, these enzymes alter chromatin conformation, thereby regulating gene expression. There's now evidence that histone acetylation increases gene transcription, and histone deacetylation reduces it. This kind of methylation by histone can enhance or suppress gene expression depending on the place of modification. H3K79me1/2, for instance, is related to transcriptional activation; H3K79me3 and H3K27me3 to transcriptional inhibition. The variants of H3 include H3.1 and H3.3, most popular variants. These variants differ by only a few amino acids but they differ functionally dramatically. For instance, H3.3 is typically associated with transcriptionally active regions and plays a crucial role in cellular reprogramming. These variants are assembled by specific molecular chaperones and perform distinct biological functions within chromatin.

Figure 1. Differences between replicative histones and histone variants in human
(Source: Ray-Gallet D, et al. 2021)

One element of epigenetic regulation, the modification of histones, has been discovered to have a broad applicability to functional regulation of vascular endothelial cells. Post-translational changes in histones can control eNOS transcription and alter vascular tone by regulating NO. Conversely, when HUVECs are pumped with LPS, IL-6 is released. This IL-6 upregulation is associated with more H3K4 trimethylation in the IL-6 promoter region. TNF-α mediated endothelial inflammatory signalling through NF-κB. Histone demethylases are recruited very quickly to the NF-κB promoter site in human HUVECs by TNF-α and methylate H3K9me2 and H3K27me3, respectively, to activate the NF-κB pathway. Drug blocking histone demethylase can significantly lower adhesion molecules' expression, monocyte adhesion to endothelium, and endothelial inflammation.

Repairing DNA takes place in chromatin and chromatin, depending on its local structure, modification and arrangement, guides repair. This means that chromatin remodelling at the damage site allows effective repair, and histone modifications help in this process. The different forms of histone methylation have their own repair pathways. H3K36me3 is typically linked to homologous recombination repair. H4K20me2 promotes non-homologous end joining repair. This selectivity allows cells to effectively choose appropriate repair mechanisms based on the type of damage. Histone methylation can also alter chromatin conformation, transitioning it from a condensed state to an open state, making DNA more accessible to repair factors. This remodeling is essential for the efficient recruitment of DNA repair enzymes.