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Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Nat+Commun 2015 ; 6 (ä): ä Nephropedia Template TP
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Multivalency governs HP1? association dynamics with the silent chromatin state #MMPMID26084584
Kilic S; Bachmann AL; Bryan LC; Fierz B
Nat Commun 2015[]; 6 (ä): ä PMID26084584show ga
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 1? (HP1?), 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 HP1? residence time on chromatin depends on the density of H3K9me3, as dissociated factors can rapidly rebind at neighbouring sites. Moreover, by chemically controlling HP1? 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 HP1?. 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.