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DNA sequence-dependent formation of heterochromatin nanodomains

View ORCID ProfileGraeme J. Thorn, Christopher T. Clarkson, Anne Rademacher, Hulkar Mamayusupova, View ORCID ProfileGunnar Schotta, View ORCID ProfileKarsten Rippe, View ORCID ProfileVladimir B. Teif
doi: https://doi.org/10.1101/2020.12.20.423673
Graeme J. Thorn
1School of LIfe Sciences, University of Essex, Wivenhoe Park, Colchester, CO4 3SQ, UK
2Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK
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Christopher T. Clarkson
1School of LIfe Sciences, University of Essex, Wivenhoe Park, Colchester, CO4 3SQ, UK
3University College London, Gower St, Bloomsbury, London WC1E 6BT, UK
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Anne Rademacher
4Division of Chromatin Networks, German Cancer Research Center (DKFZ) & Bioquant, Heidelberg, 69120, Germany
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Hulkar Mamayusupova
1School of LIfe Sciences, University of Essex, Wivenhoe Park, Colchester, CO4 3SQ, UK
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Gunnar Schotta
5Ludwig-Maximilians-Universität München, Geschwister-Scholl-Platz 1, 80539 München, Germany
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Karsten Rippe
4Division of Chromatin Networks, German Cancer Research Center (DKFZ) & Bioquant, Heidelberg, 69120, Germany
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  • For correspondence: vteif@essex.ac.uk karsten.rippe@dkfz.de
Vladimir B. Teif
1School of LIfe Sciences, University of Essex, Wivenhoe Park, Colchester, CO4 3SQ, UK
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  • ORCID record for Vladimir B. Teif
  • For correspondence: vteif@essex.ac.uk karsten.rippe@dkfz.de
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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.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted December 21, 2020.
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DNA sequence-dependent formation of heterochromatin nanodomains
Graeme J. Thorn, Christopher T. Clarkson, Anne Rademacher, Hulkar Mamayusupova, Gunnar Schotta, Karsten Rippe, Vladimir B. Teif
bioRxiv 2020.12.20.423673; doi: https://doi.org/10.1101/2020.12.20.423673
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DNA sequence-dependent formation of heterochromatin nanodomains
Graeme J. Thorn, Christopher T. Clarkson, Anne Rademacher, Hulkar Mamayusupova, Gunnar Schotta, Karsten Rippe, Vladimir B. Teif
bioRxiv 2020.12.20.423673; doi: https://doi.org/10.1101/2020.12.20.423673

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