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Nucleic Acids Res. 2019 Sep 19;47(16):8470-8484. doi: 10.1093/nar/gkz593.

Super-resolution microscopy reveals how histone tail acetylation affects DNA compaction within nucleosomes in vivo.

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ICFO-Institute of Photonic Sciences, Barcelona Institute of Science and Technology, Barcelona.
Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona 08003, Spain.
Universitat Pompeu Fabra (UPF), Barcelona, Spain.
ICREA, Pg. Lluis Companys 23, Barcelona 08010, Spain.
Guangzhou Regenerative Medicine and Health Guangdong Laboratory (GRMH-GDL), Guangzhou 510005, China.
Key Laboratory of Regenerative Biology and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Science, Guangzhou 510530, China.
Perelman School of Medicine, Department of Physiology, University of Pennsylvania, Clinical Research Building, 415 Curie Boulevard, Philadelphia, PA 19104, USA.


Chromatin organization is crucial for regulating gene expression. Previously, we showed that nucleosomes form groups, termed clutches. Clutch size correlated with the pluripotency grade of mouse embryonic stem cells and human induced pluripotent stem cells. Recently, it was also shown that regions of the chromatin containing activating epigenetic marks were composed of small and dispersed chromatin nanodomains with lower DNA density compared to the larger silenced domains. Overall, these results suggest that clutch size may regulate DNA packing density and gene activity. To directly test this model, we carried out 3D, two-color super-resolution microscopy of histones and DNA with and without increased histone tail acetylation. Our results showed that lower percentage of DNA was associated with nucleosome clutches in hyperacetylated cells. We further showed that the radius and compaction level of clutch-associated DNA decreased in hyperacetylated cells, especially in regions containing several neighboring clutches. Importantly, this change was independent of clutch size but dependent on the acetylation state of the clutch. Our results directly link the epigenetic state of nucleosome clutches to their DNA packing density. Our results further provide in vivo support to previous in vitro models that showed a disruption of nucleosome-DNA interactions upon hyperacetylation.

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