H1 histones control the epigenetic landscape by local chromatin compaction Journal Article

Authors: Willcockson, M. A.; Healton, S. E.; Weiss, C. N.; Bartholdy, B. A.; Botbol, Y.; Mishra, L. N.; Sidhwani, D. S.; Wilson, T. J.; Pinto, H. B.; Maron, M. I.; Skalina, K. A.; Toro, L. N.; Zhao, J.; Lee, C. H.; Hou, H.; Yusufova, N.; Meydan, C.; Osunsade, A.; David, Y.; Cesarman, E.; Melnick, A. M.; Sidoli, S.; Garcia, B. A.; Edelmann, W.; Macian, F.; Skoultchi, A. I.
Article Title: H1 histones control the epigenetic landscape by local chromatin compaction
Abstract: H1 linker histones are the most abundant chromatin-binding proteins1. In vitro studies indicate that their association with chromatin determines nucleosome spacing and enables arrays of nucleosomes to fold into more compact chromatin structures. However, the in vivo roles of H1 are poorly understood2. Here we show that the local density of H1 controls the balance of repressive and active chromatin domains by promoting genomic compaction. We generated a conditional triple-H1-knockout mouse strain and depleted H1 in haematopoietic cells. H1 depletion in T cells leads to de-repression of T cell activation genes, a process that mimics normal T cell activation. Comparison of chromatin structure in normal and H1-depleted CD8+ T cells reveals that H1-mediated chromatin compaction occurs primarily in regions of the genome containing higher than average levels of H1: the chromosome conformation capture (Hi-C) B compartment and regions of the Hi-C A compartment marked by PRC2. Reduction of H1 stoichiometry leads to decreased H3K27 methylation, increased H3K36 methylation, B-to-A-compartment shifting and an increase in interaction frequency between compartments. In vitro, H1 promotes PRC2-mediated H3K27 methylation and inhibits NSD2-mediated H3K36 methylation. Mechanistically, H1 mediates these opposite effects by promoting physical compaction of the chromatin substrate. Our results establish H1 as a critical regulator of gene silencing through localized control of chromatin compaction, 3D genome organization and the epigenetic landscape. © 2020, The Author(s), under exclusive licence to Springer Nature Limited.
Keywords: adult; controlled study; unclassified drug; nonhuman; comparative study; cd8+ t lymphocyte; animal cell; mouse; animal tissue; protein depletion; animal experiment; protein interaction; in vitro study; genome analysis; epigenetics; histone methyltransferase; gene repression; hematopoietic cell; gene control; autosome; t lymphocyte activation; chromatin structure; stoichiometry; dna conformation; histone methylation; histone h1; polycomb repressive complex 2; male; female; priority journal; article; protein nsd2
Journal Title: Nature
Volume: 589
Issue: 7841
ISSN: 0028-0836
Publisher: Nature Publishing Group  
Date Published: 2021-01-14
Start Page: 293
End Page: 298
Language: English
DOI: 10.1038/s41586-020-3032-z
PUBMED: 33299182
PROVIDER: scopus
Notes: Article -- Export Date: 1 February 2021 -- Source: Scopus
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