Multivalency governs HP1α association dynamics with the silent chromatin state

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Multivalent interactions between effector proteins and histone post-translational modifications are an elementary mechanism of dynamic chromatin signalling. Here we elucidate the mechanism how heterochromatin protein 1α (HP1α), a multivalent effector, is efficiently recruited to the silent chromatin state (marked by trimethylated H3 at Lys9, H3K9me3) while remaining highly dynamic. Employing chemically defined nucleosome arrays together with single-molecule total internal reflection fluorescence microscopy (smTIRFM), we demonstrate that the HP1α residence time on chromatin depends on the density of H3K9me3, as dissociated factors can rapidly rebind at neighbouring sites. Moreover, by chemically controlling HP1α dimerization we find that effector multivalency prolongs chromatin retention and, importantly, accelerates the association rate. This effect results from increased avidity together with strengthened nonspecific chromatin interactions of dimeric HP1α. We propose that accelerated chromatin binding is a key feature of effector multivalency, allowing for fast and efficient competition for binding sites in the crowded nuclear compartment.

Original languageEnglish
Article number7313
JournalNature Communications
Volume6
ISSN2041-1723
DOIs
Publication statusPublished - 18 Jun 2015
Externally publishedYes

Bibliographical note

Funding Information:
We thank Joachim Piquet, Horst Vogel and Daniel Ciepielewski (Nikon CH) for help with setting up the TIRF microscope, Aleksandr Benke, Seamus J. Holden and Suliana Manley for help with initial experiments, Carolin Lechner for assistance with peptide synthesis, Horst Pick for help with cell culture, Arne Seitz and Thierry Laroche (BIOP, EPFL) for assistance with the FRAP experiments, Horst Vogel, Champak Chatterjee, Kai Johnsson and all members of LCBM for fruitful discussions and comments on the manuscript. For financial support we thank the Sandoz Family Foundation, the Swiss National Science Foundation (grant 31003A_149789) and EPFL. S.K. is kindly supported by a fellowship from the Boehringer Ingelheim Fonds.

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