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bioRxiv · 10.1101/2020.12.20.423673

DNA sequence-dependent formation of heterochromatin nanodomains

Thorn, G. J.·Clarkson, C. T.·Rademacher, A.·Mamayusupova, H.·Schotta, G.·Rippe, K.·Teif, V. B.
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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, which have a typical size of 3-10 nucleosomes. However, the (epi)genetic determinants of their location and boundaries are only partly understood. Here, we compare 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. Based on a novel chromatin hierarchical lattice framework termed ChromHL, we are able to predict HND maps with singe-nucleotide resolution. We find that HND nucleation can be rationalized by DNA sequence specific protein binding to PAX3/9, ADNP and LINE1 repeats. Depending on type of microdomains, boundaries are determined either by CTCF binding sites or by nucleosome-nucleosome and nucleosome-HP1 interactions. Our new framework allows predicting how patterns of H3K9me2/3 and other chromatin nanodomains are established and changed in processes such as cell differentiation.

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Thorn, G. J., Clarkson, C. T., Rademacher, A., Mamayusupova, H., Schotta, G., Rippe, K., Teif, V. B.. 2020-12-21. DNA sequence-dependent formation of heterochromatin nanodomains. https://doi.org/10.1101/2020.12.20.423673

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