June 2019 : Chromatin condensation fluctuations rather than steady-state predict chromatin accessibility

Chromatin accessibility to protein factors is critical for genome activities. However, the dynamic properties of chromatin higher-order structures that regulate its accessibility are poorly understood. Researchers from the team “mechanotransduction: from cell surface to nucleus” took advantage of the microenvironment sensitivity of the fluorescence lifetime of EGFP-H4 histone incorporated in chromatin to map in the nucleus of live cells the dynamics of chromatin condensation and its direct interaction with a tail acetylation recognition domain (the double bromodomain module of human TAFII250, dBD). They revealed chromatin condensation fluctuations supported by mechanisms fundamentally distinct from that of condensation. Fluctuations are spontaneous, yet their amplitudes are affected by their sub-nuclear localization and by competing mechanisms dependent on histone acetylation, ATP and both. Moreover, accessibility of acetylated histone H4 to dBD is not restricted by chromatin condensation nor predicted by acetylation, rather, it is predicted by chromatin condensation fluctuations.

Legend: Mechanisms regulating spontaneous fluctuations of chromatin condensation. TF: transcription factor, RF: ATP-dependent and acetylation-binding remodeling factor and its state (active/inactive, Ac bound or not). Plain circle: same-condensation domain size, dashed circle: same accessibility domain size.

To know more:
Chromatin condensation fluctuations rather than steady-state predict chromatin accessibility.
Audugé N, Padilla-Parra S, Tramier M, Borghi N, Coppey-Moisan M.
Nucleic Acids Res. 2019 May 13. pii: gkz373. doi: 10.1093/nar/gkz373.

Contact: nicolas.borghi(at)ijm.fr and maite.coppey(at)ijm.fr,  team: Mechanotransduction: from cell surface to nucleus.

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