PT  - JOURNAL ARTICLE
AU  - Nicolas Audugé
AU  - Sergi Padilla-Parra
AU  - Marc Tramier
AU  - Nicolas Borghi
AU  - Maïté Coppey-Moisan
TI  - Chromatin Condensation Fluctuations Rather than Steady-State Predict Chromatin Accessibility
AID  - 10.1101/365700
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 365700
4099  - http://biorxiv.org/content/early/2018/07/09/365700.short
4100  - http://biorxiv.org/content/early/2018/07/09/365700.full
AB  - Chromatin accessibility to protein factors is critical for genome activities. Dynamic changes in nucleosomal DNA compaction and higher order chromatin structures are expected to allow specific sites to be accessible to regulatory factors and the transcriptional machinery. However, the dynamic properties of chromatin that regulate its accessibility are poorly understood. Here, we 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). We reveal 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 distinct and competing mechanisms dependent on histone acetylation, ATP, and both. Moreover, we show that 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.Significance In higher eukaryotes, the structure and compaction of chromatin are considered as barriers to genome activities. Epigenetic marks such as post-translational modifications of histones can modify the structure and compaction of chromatin. The accessibility of protein factors to these epigenetic marks is therefore of paramount importance for genome activities. We reveal chromatin condensation fluctuations supported by mechanisms fundamentally distinct from that of condensation itself. We show that accessibility of acetylated histone H4 to double bromodomains is not restricted by chromatin condensation nor predicted by acetylation, rather, it is predicted by chromatin condensation fluctuations.Classification Biological Sciences, Cell BiologyAuthor contributionsN.A., S.P.-P., M.T. performed experiments; N.A., S.P.-P., M.T. Developed methodology; N.A. N.B. and M.C.-M. analyzed data; M.C.-M. supervised research; N.B. and M.C.-M. wrote the manuscript.