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Revealing chromatin state organization on the single‐molecule scale
Author(s) -
Fierz Beat
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.523.4
Subject(s) - chromatin , scale (ratio) , state (computer science) , computational biology , chemistry , physics , biology , computer science , dna , quantum mechanics , biochemistry , algorithm
The elucidation of the structure and dynamics of chromatin is a problem spanning orders of magnitude in spatial (Å to micrometers) and temporal (microseconds to hours) scales. Chromatin structure and dynamics control access to the DNA. It is thus tightly controlled by effector proteins, which are recruited by patterns of post‐translational modifications (PTMs) on the histone proteins. Together, the dynamic architecture of chromatin fibers in complex with effector proteins is however poorly understood, due to a lack of methods suitable to study large heterogeneous complexes. We combine chemical chromatin synthesis and single‐molecule imaging to study how multivalent chromatin effectors dynamically interact with modified chromatin and establish a chromatin state. Employing single‐molecule colocalization imaging, we dissected the chromatin interaction dynamics of defining components of facultative and constitutive heterochromatin, PRC2 and HP1. These studies revealed how non‐specific DNA interactions work together with multivalent histone PTM recognition in dynamic chromatin organization. Concurrently, we are using multimodal single‐molecule Förster resonance energy transfer (smFRET) approaches to observe chromatin fiber structure and dynamics. Imaging single chromatin fibers, we could characterize the underlying structural states and their interconversion kinetics from microseconds to seconds. In this context, HP1 proteins induced a dynamically compacted state that exhibited structural fluctuations on its binding timescales. In summary, our studies reveal that chromatin fibers form dynamic and highly multivalent complexes with effector proteins, establishing a dynamic chromatin state that controls gene function. Support or Funding Information Swiss National Science Foundation (grant 31003A_173169) European Research Council through the Consolidator Grant 2017 chromo‐SUMMIT (724022) EPFLThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .