PT  - JOURNAL ARTICLE
AU  - Graeme J. Thorn
AU  - Christopher T. Clarkson
AU  - Anne Rademacher
AU  - Hulkar Mamayusupova
AU  - Gunnar Schotta
AU  - Karsten Rippe
AU  - Vladimir B. Teif
TI  - DNA sequence-dependent formation of heterochromatin nanodomains
AID  - 10.1101/2020.12.20.423673
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.12.20.423673
4099  - http://biorxiv.org/content/early/2020/12/21/2020.12.20.423673.short
4100  - http://biorxiv.org/content/early/2020/12/21/2020.12.20.423673.full
AB  - 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.Competing Interest StatementThe authors have declared no competing interest.