Histone H3 K36M Mutant/H3K36M [RM193]

Histone H3 is one of the five main histone proteins involved in the structure of chromatin in eukaryotic cells. Featuring a main globular domain and a long N-terminal tail, H3 is involved with the structure of the nucleosomes of the ‘beads on a string’ structure. The N-terminal tail of histone H3 protrudes from the globular nucleosome core and can undergo several different types of epigenetic modifications that influence cellular processes. These modifications include the covalent attachment of methyl or acetyl groups to lysine and arginine amino acids and the phosphorylation of serine or threonine. Histone H3 variants (H3.1, H3.2 and H3.3) have been implicated in the epigenetic memory of cellular state. Genome-wide patterns of H3 are dependent on amino acid sequence and change with cellular differentiation at developmentally regulated loci. Somatic missense mutations in histone H3 genes are found in several pediatric brain and bone malignancies, among which ~90% of the chondroblastomas are identified with histone H3 K36M mutation (H3K36M). Loss of H3K36 methylation due to H3K36M mutation causes a genome-wide upregulation of H3K27 methylation, leading to an altered polycomb repressive complex 1 (PRC1) distribution and re-activation of PRC1-suppressed target genes involved in mesenchymal differentiation.