Thorn, Graeme J and Clarkson, Christopher T and Rademacher, Anne and Mamayusupova, Hulkar and Schotta, Gunnar and Rippe, Karsten and Teif, Vladimir B (2022) 'DNA sequence-dependent formation of heterochromatin nanodomains.' Nature Communications, 13 (1). 1861-. ISSN 2041-1723

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Abstract

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 Type:	Article
Uncontrolled Keywords:	Chromatin; Heterochromatin; Nucleosomes; Animals; Mice; Homeodomain Proteins; Nerve Tissue Proteins; Chromosomal Proteins, Non-Histone; Histones; Base Sequence; Chromobox Protein Homolog 5
Divisions:	Faculty of Science and Health Faculty of Science and Health > Life Sciences, School of
SWORD Depositor:	Elements
Depositing User:	Elements
Date Deposited:	25 Apr 2022 12:44
Last Modified:	28 Apr 2022 07:11
URI:	http://repository.essex.ac.uk/id/eprint/32753

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