» Articles » PMID: 26238434

Spatiotemporal Regulation of Heterochromatin Protein 1-alpha Oligomerization and Dynamics in Live Cells

Overview
Journal Sci Rep
Specialty Science
Date 2015 Aug 5
PMID 26238434
Citations 14
Authors
Affiliations
Soon will be listed here.
Abstract

Heterochromatin protein 1 (HP1) is a central factor in establishing and maintaining the heterochromatin state. As consequence of playing a structural role in heterochromatin, HP1 proteins can have both an activating as well as repressive function in gene expression. Here we probe how oligomerisation of the HP1-α isoform modulates interaction with chromatin, by spatially resolved fluorescence correlation spectroscopy (FCS). We find from fluctuation analysis of HP1-α dynamics that this isoform exists as a dimer around the periphery of heterochromatin foci and these foci locally rotate with characteristic turn rates that range from 5-100 ms. From inhibition of HP1-α homo-oligomerization we find the slow turn rates (20-100 ms) are dimer dependent. From treatment with drugs that disrupt or promote chromatin compaction, we find that HP1-α dimers spatially redistribute to favor fast (5-10 ms) or slow (20-100 ms) turn rates. Collectively our results demonstrate HP1-α oligomerization is critical to the maintenance of heterochromatin and the tunable dynamics of this HP1 isoform.

Citing Articles

Pair correlation microscopy of intracellular molecular transport.

Sanchez-Velasquez J, Solano A, Digman M, Gratton E, Cardarelli F, Hinde E Nat Protoc. 2025; .

PMID: 39915621 DOI: 10.1038/s41596-024-01097-6.


Clr4 ubiquitination and non-coding RNA mediate transcriptional silencing of heterochromatin via Swi6 phase separation.

Kim H, Roche B, Bhattacharjee S, Todeschini L, Chang A, Hammell C Nat Commun. 2024; 15(1):9384.

PMID: 39477922 PMC: 11526040. DOI: 10.1038/s41467-024-53417-9.


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 C, Das A, Bediaga N Nucleic Acids Res. 2024; 52(18):10918-10933.

PMID: 39193905 PMC: 11472067. DOI: 10.1093/nar/gkae720.


Tracking live-cell single-molecule dynamics enables measurements of heterochromatin-associated protein-protein interactions.

Chen Z, Seman M, Fyodorova Y, Farhat A, Ames A, Levashkevich A Nucleic Acids Res. 2024; 52(18):10731-10746.

PMID: 39142658 PMC: 11472046. DOI: 10.1093/nar/gkae692.


The dynamical organization of the core pluripotency transcription factors responds to differentiation cues in early S-phase.

Oses C, Francia M, Verneri P, Vazquez Echegaray C, Guberman A, Levi V Front Cell Dev Biol. 2023; 11:1125015.

PMID: 37215075 PMC: 10192714. DOI: 10.3389/fcell.2023.1125015.


References
1.
JONES D, Cowell I, Singh P . Mammalian chromodomain proteins: their role in genome organisation and expression. Bioessays. 2000; 22(2):124-37. DOI: 10.1002/(SICI)1521-1878(200002)22:2<124::AID-BIES4>3.0.CO;2-E. View

2.
Smothers J, Henikoff S . The HP1 chromo shadow domain binds a consensus peptide pentamer. Curr Biol. 2000; 10(1):27-30. DOI: 10.1016/s0960-9822(99)00260-2. View

3.
Brasher S, Smith B, Fogh R, Nietlispach D, Thiru A, Nielsen P . The structure of mouse HP1 suggests a unique mode of single peptide recognition by the shadow chromo domain dimer. EMBO J. 2000; 19(7):1587-97. PMC: 310228. DOI: 10.1093/emboj/19.7.1587. View

4.
Cowieson N, Partridge J, Allshire R, McLaughlin P . Dimerisation of a chromo shadow domain and distinctions from the chromodomain as revealed by structural analysis. Curr Biol. 2000; 10(9):517-25. DOI: 10.1016/s0960-9822(00)00467-x. View

5.
Minc E, Courvalin J, Buendia B . HP1gamma associates with euchromatin and heterochromatin in mammalian nuclei and chromosomes. Cytogenet Cell Genet. 2000; 90(3-4):279-84. DOI: 10.1159/000056789. View