Heterochromatin protein 1 alpha (HP1α) undergoes a monomer to dimer transition that opens and compacts live cell genome architecture

Lou, J; Deng, Q; Zhang, X; Bell, CC; Das, AB; Bediaga, NG; Zlatic, CO; Johanson, TM; Allan, RS; Griffin, MDW; Paradkar, P; Harvey, KF; Dawson, MA; Hinde, E

Author(s): Lou, J; Deng, Q; Zhang, X; Bell, CC; Das, AB; Bediaga, NG; Zlatic, CO; Johanson, TM; Allan, RS; Griffin, MDW; Paradkar, P; Harvey, KF; Dawson, MA; Hinde, E;
Details: Publication Year 2024-08-28,Volume 52,Issue #18,Page 10918-10933
Journal Title: Nucleic Acids Research
Abstract: Our understanding of heterochromatin nanostructure and its capacity to mediate gene silencing in a living cell has been prevented by the diffraction limit of optical microscopy. Thus, here to overcome this technical hurdle, and directly measure the nucleosome arrangement that underpins this dense chromatin state, we coupled fluorescence lifetime imaging microscopy (FLIM) of Förster resonance energy transfer (FRET) between histones core to the nucleosome, with molecular editing of heterochromatin protein 1 alpha (HP1α). Intriguingly, this super-resolved readout of nanoscale chromatin structure, alongside fluorescence fluctuation spectroscopy (FFS) and FLIM-FRET analysis of HP1α protein-protein interaction, revealed nucleosome arrangement to be differentially regulated by HP1α oligomeric state. Specifically, we found HP1α monomers to impart a previously undescribed global nucleosome spacing throughout genome architecture that is mediated by trimethylation on lysine 9 of histone H3 (H3K9me3) and locally reduced upon HP1α dimerisation. Collectively, these results demonstrate HP1α to impart a dual action on chromatin that increases the dynamic range of nucleosome proximity. We anticipate that this finding will have important implications for our understanding of how live cell heterochromatin structure regulates genome function.
Publisher: Oxford Academic
Keywords: *Chromobox Protein Homolog 5; *Chromosomal Proteins, Non-Histone/metabolism/chemistry/genetics; Humans; *Nucleosomes/metabolism/chemistry/genetics; *Histones/metabolism/chemistry/genetics; *Heterochromatin/metabolism/chemistry/genetics; *Protein Multimerization; Fluorescence Resonance Energy Transfer; Microscopy, Fluorescence; Chromatin/metabolism/chemistry/genetics; Methylation
Research Division(s): Immunology
PubMed ID: 39193905
Publisher's Version: https://doi.org/10.1093/nar/gkae720
Open Access at Publisher's Site: https://doi.org/10.1093/nar/gkae720
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-09-02 10:42:08

Last Modified: 2024-10-25 10:50:50