Single-molecule kinetic analysis of HP1-chromatin binding reveals a dynamic network of histone modification and DNA interactions.

Autor:	Bryan LC; Laboratory of Biophysical Chemistry of Macromolecules, Institute of Chemical Sciences and Engineering (ISIC), Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland., Weilandt DR; Laboratory of Computational Systems Biotechnology, ISIC, EPFL, 1015 Lausanne, Switzerland., Bachmann AL; Laboratory of Biophysical Chemistry of Macromolecules, Institute of Chemical Sciences and Engineering (ISIC), Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland., Kilic S; Laboratory of Biophysical Chemistry of Macromolecules, Institute of Chemical Sciences and Engineering (ISIC), Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland., Lechner CC; Laboratory of Biophysical Chemistry of Macromolecules, Institute of Chemical Sciences and Engineering (ISIC), Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland., Odermatt PD; Laboratory for Bio- and Nano instrumentation, Institute of Bioengineering, EPFL, 1015 Lausanne, Switzerland., Fantner GE; Laboratory for Bio- and Nano instrumentation, Institute of Bioengineering, EPFL, 1015 Lausanne, Switzerland., Georgeon S; ISREC foundation chair in translational oncology, School of Life Sciences, EPFL, 1015 Lausanne, Switzerland., Hantschel O; ISREC foundation chair in translational oncology, School of Life Sciences, EPFL, 1015 Lausanne, Switzerland., Hatzimanikatis V; Laboratory of Computational Systems Biotechnology, ISIC, EPFL, 1015 Lausanne, Switzerland., Fierz B; Laboratory of Biophysical Chemistry of Macromolecules, Institute of Chemical Sciences and Engineering (ISIC), Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
Jazyk:	angličtina
Zdroj:	Nucleic acids research [Nucleic Acids Res] 2017 Oct 13; Vol. 45 (18), pp. 10504-10517.
DOI:	10.1093/nar/gkx697
Abstrakt:	Chromatin recruitment of effector proteins involved in gene regulation depends on multivalent interaction with histone post-translational modifications (PTMs) and structural features of the chromatin fiber. Due to the complex interactions involved, it is currently not understood how effectors dynamically sample the chromatin landscape. Here, we dissect the dynamic chromatin interactions of a family of multivalent effectors, heterochromatin protein 1 (HP1) proteins, using single-molecule fluorescence imaging and computational modeling. We show that the three human HP1 isoforms are recruited and retained on chromatin by a dynamic exchange between histone PTM and DNA bound states. These interactions depend on local chromatin structure, the HP1 isoforms as well as on PTMs on HP1 itself. Of the HP1 isoforms, HP1α exhibits the longest residence times and fastest binding rates due to DNA interactions in addition to PTM binding. HP1α phosphorylation further increases chromatin retention through strengthening of multivalency while reducing DNA binding. As DNA binding in combination with specific PTM recognition is found in many chromatin effectors, we propose a general dynamic capture mechanism for effector recruitment. Multiple weak protein and DNA interactions result in a multivalent interaction network that targets effectors to a specific chromatin modification state, where their activity is required. (© The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Databáze:	MEDLINE
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