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DNA sequence-dependent heterochromatin microdomain formation

ABSTRACT: Cell-type specific gene expression programs are established by distinct chromatin state patterns that involve thousands of heterochromatin microdomains of ~1-2 kb in size marked by di- and trimethylation of histone H3 at lysine 9 (H3K9me2/me3). However, no theoretical framework exists to predict the location and boundaries of such domains from the DNA sequence. Here, we compare H3K9me2/me3-heterochromatin microdomains in mouse embryonic stem cells (ESCs) that are dependent on the histone methylases SUV39H1/2 and GLP, transcription factor ADNP or chromatin remodeler ATRX. By applying a novel Ising-type chromatin hierarchical lattice (ChromHL) model, we identify two different microdomain types that are distinct with respect to their dependence on DNA sequence motifs or nucleosome interactions. ChromHL is able to predict microdomain location, extension and boundaries based on binding sites of PAX3, PAX9, ADNP, CTCF and repeat sequence motifs, the concentration of heterochromatin protein 1 (HP1) and the strength of nucleosome-nucleosome interactions. Thus, our result provides insight how distinct patterns of silenced heterochromatin states are implemented and regulated.

ORGANISM(S): Mus musculus

PROVIDER: GSE158744 | GEO | 2022/02/07

REPOSITORIES: GEO

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