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DNA sequence-dependent formation of heterochromatin nanodomains

The mammalian epigenome contains thousands of heterochromatin nanodomains (HNDs) marked by di- and trimethylation of histone H3 at lysine 9 (H3K9me2/3), which have a typical size of 3-10 nucleosomes. However, what governs HND location and extension is only partly understood. Here, we address this is...

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Main Authors: Thorn, Graeme J. (Author) , Clarkson, Christopher T. (Author) , Rademacher, Anne (Author) , Mamayusupova, Hulkar (Author) , Schotta, Gunnar (Author) , Rippe, Karsten (Author) , Teif, Vladimir B. (Author)
Format: Article (Journal)
Language:English
Published: 06 April 2022
In: Nature Communications
Year: 2022, Volume: 13, Pages: 1-13
ISSN:2041-1723
DOI:10.1038/s41467-022-29360-y
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s41467-022-29360-y
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/s41467-022-29360-y
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Author Notes:Graeme J. Thorn, Christopher T. Clarkson, Anne Rademacher, Hulkar Mamayusupova, Gunnar Schotta, Karsten Rippe & Vladimir B. Teif
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Summary:The mammalian epigenome contains thousands of heterochromatin nanodomains (HNDs) marked by di- and trimethylation of histone H3 at lysine 9 (H3K9me2/3), which have a typical size of 3-10 nucleosomes. However, what governs HND location and extension is only partly understood. Here, we address this issue by introducing the chromatin hierarchical lattice framework (ChromHL) that predicts chromatin state patterns with single-nucleotide resolution. ChromHL is applied to analyse four HND types in mouse embryonic stem cells that are defined by histone methylases SUV39H1/2 or GLP, transcription factor ADNP or chromatin remodeller ATRX. We find that HND patterns can be computed from PAX3/9, ADNP and LINE1 sequence motifs as nucleation sites and boundaries that are determined by DNA sequence (e.g. CTCF binding sites), cooperative interactions between nucleosomes as well as nucleosome-HP1 interactions. Thus, ChromHL rationalizes how patterns of H3K9me2/3 are established and changed via the activity of protein factors in processes like cell differentiation.
Item Description:Gesehen am 17.05.2022
Physical Description:Online Resource
ISSN:2041-1723
DOI:10.1038/s41467-022-29360-y

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