Heterotypic [H3K4me3 • H3K9,14,18ac] Recombinant Nucleosome, Biotinylated

Heterotypic nucleosomes, also referred to as “asymmetric nucleosomes,” contain sister histones with distinct histone variants
and/or post-translational modifications (PTMs). In homotypic nucleosomes, or “symmetric nucleosomes,” each pair of sister
histones bears the same PTM, set of PTMs, or histone variant. Histone-modifying enzymes, chromatin remodelers, and histone
chaperones differentially modify sister histones or exchange unique histone variants to form heterotypic nucleosomes.
Heterotypic nucleosomes have been found at promoters of developmental genes in undifferentiated embryonic stem cells and
transcription start sites (TSSs) of approximately half of the genes in budding yeast [1]. Heterotypic nucleosomes represent an
additional layer of the histone code, acting as substrates for multivalent reader proteins, participating in PTM crosstalk
mechanisms, and influencing reader protein binding affinity through varying local target concentration. Recombinant
heterotypic nucleosomes are useful for studying chromatin dynamics and transcriptional regulation.

Heterotypic [H3K4me3 • H3K9,14,18ac] Recombinant Nucleosome, Biotinylated is a fully defined semi-synthetic nucleosome
containing combinatorial PTMs in both cis and trans whereby one histone H3 is trimethylated at lysine four while the other is
acetylated at lysines 9, 14, and 18. [H3K4me3 • H3K9,14,18ac] nucleosome consists of 147 base pairs of 601 sequence DNA
[2] wrapped around an octamer of core histone proteins (two each of H2A, H2B, H3.2, and H4) to form a nucleosome, the
basic repeating unit of chromatin. The DNA contains a 5’ biotin-TEG group, and histone H3.2 has a Cys to Ala substitution at
position 110. H3 hyperacetylation in cis (e.g. H3K9,14,18ac) increases tail accessibility for H3K4 methyl writers such as the
methyltransferase MLL1, emphasizing the role of PTM crosstalk and heterotypic nucleosomes in chromatin regulatory
mechanisms [3].