Engineered Multivalent Sensors to Detect Coexisting Histone Modifications in Living Stem Cells.

Autor:	Delachat AM; Laboratory of Biophysical Chemistry of Macromolecules (LCBM), Institute of Chemical Sciences and Engineering (ISIC), Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland., Guidotti N; Laboratory of Biophysical Chemistry of Macromolecules (LCBM), Institute of Chemical Sciences and Engineering (ISIC), Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland., Bachmann AL; Laboratory of Biophysical Chemistry of Macromolecules (LCBM), Institute of Chemical Sciences and Engineering (ISIC), Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland., Meireles-Filho ACA; Laboratory of Systems Biology and Genetics, Institute of Bioengineering (IBI), School of Life Sciences, EPFL and Swiss Institute of Bioinformatics (SIB), 1015 Lausanne, Switzerland., Pick H; Laboratory of Biophysical Chemistry of Macromolecules (LCBM), Institute of Chemical Sciences and Engineering (ISIC), Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland., Lechner CC; Laboratory of Biophysical Chemistry of Macromolecules (LCBM), Institute of Chemical Sciences and Engineering (ISIC), Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland., Deluz C; UPSUTER, IBI, School of Life Sciences, EPFL, 1015 Lausanne, Switzerland., Deplancke B; Laboratory of Systems Biology and Genetics, Institute of Bioengineering (IBI), School of Life Sciences, EPFL and Swiss Institute of Bioinformatics (SIB), 1015 Lausanne, Switzerland., Suter DM; UPSUTER, IBI, School of Life Sciences, EPFL, 1015 Lausanne, Switzerland., Fierz B; Laboratory of Biophysical Chemistry of Macromolecules (LCBM), Institute of Chemical Sciences and Engineering (ISIC), Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland. Electronic address: beat.fierz@epfl.ch.
Jazyk:	angličtina
Zdroj:	Cell chemical biology [Cell Chem Biol] 2018 Jan 18; Vol. 25 (1), pp. 51-56.e6. Date of Electronic Publication: 2017 Nov 22.
DOI:	10.1016/j.chembiol.2017.10.008
Abstrakt:	The regulation of fundamental processes such as gene expression or cell differentiation involves chromatin states, demarcated by combinatorial histone post-translational modification (PTM) patterns. The subnuclear organization and dynamics of chromatin states is not well understood, as tools for their detection and modulation in live cells are lacking. Here, we report the development of genetically encoded chromatin-sensing multivalent probes, cMAPs, selective for bivalent chromatin, a PTM pattern associated with pluripotency in embryonic stem cells (ESCs). cMAPs were engineered from a set of PTM-binding (reader) proteins and optimized using synthetic nucleosomes carrying defined PTMs. Applied in live ESCs, cMAPs formed discrete subnuclear foci, revealing the organization of bivalent chromatin into local clusters. Moreover, cMAPs enabled direct monitoring of the loss of bivalency upon treatment with small-molecule epigenetic modulators. cMAPs thus provide a versatile platform to monitor chromatin state dynamics in live cells. (Copyright © 2017 Elsevier Ltd. All rights reserved.)
Databáze:	MEDLINE
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