DNA sequence-dependent formation of heterochromatin nanodomains

• DOI: 10.1038/s41467-022-29360-y
• Publication Date: 2022-04-06T10:08:13Z
• Authors: Graeme J. Thorn; Christopher T. Cl...; Anne Rademacher; Hulkar Mamayusupova; Gunnar Schotta; Karsten Rippe; Vladimir B. Teif
• Keywords: Sequence (biology); Heterochromatin protein 1; Repeated sequence

Abstract The mammalian epigenome contains thousands of heterochromatin nanodomains (HNDs) marked by di- and trimethylation histone H3 at lysine 9 (H3K9me2/3), which have a typical size 3–10 nucleosomes. However, what governs HND location extension is only partly understood. Here, we address this issue introducing the chromatin hierarchical lattice framework (ChromHL) that predicts state patterns with single-nucleotide resolution. ChromHL applied to analyse four types in mouse embryonic stem cells are defined methylases SUV39H1/2 or GLP, transcription factor ADNP remodeller ATRX. We find can be computed from PAX3/9, LINE1 sequence motifs as nucleation sites boundaries determined DNA (e.g. CTCF binding sites), cooperative interactions between nucleosomes well nucleosome-HP1 interactions. Thus, rationalizes how H3K9me2/3 established changed via activity protein factors processes like cell differentiation.