Chromatin Fibers Are Formed by Heterogeneous Groups of Nucleosomes In Vivo

Nucleosomes help structure chromosomes by compacting DNA into fibers. To gain insight into how nucleosomes are arranged in vivo, we combined quantitative super-resolution nanoscopy with computer simulations to visualize and count nucleosomes along the chromatin fiber in single nuclei. Nucleosomes as...

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Bibliographic Details
Published in:Cell 2015-03, Vol.160 (6), p.1145-1158
Main Authors: Ricci, Maria Aurelia, Manzo, Carlo, García-Parajo, María Filomena, Lakadamyali, Melike, Cosma, Maria Pia
Format: Article
Language:English
Subjects:
Animals
Cell Differentiation
Chromatin - chemistry
Chromatin - metabolism
Computer Simulation
Embryonic Stem Cells - chemistry
Embryonic Stem Cells - metabolism
Genome-Wide Association Study
Histones - metabolism
Humans
Interphase
Mice
Mutation
Nucleosomes - chemistry
Nucleosomes - metabolism
Nucleosomes - ultrastructure
Pluripotent Stem Cells - chemistry
Pluripotent Stem Cells - metabolism
RNA Polymerase II - metabolism
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Summary:Nucleosomes help structure chromosomes by compacting DNA into fibers. To gain insight into how nucleosomes are arranged in vivo, we combined quantitative super-resolution nanoscopy with computer simulations to visualize and count nucleosomes along the chromatin fiber in single nuclei. Nucleosomes assembled in heterogeneous groups of varying sizes, here termed “clutches,” and these were interspersed with nucleosome-depleted regions. The median number of nucleosomes inside clutches and their compaction defined as nucleosome density were cell-type-specific. Ground-state pluripotent stem cells had, on average, less dense clutches containing fewer nucleosomes and clutch size strongly correlated with the pluripotency potential of induced pluripotent stem cells. RNA polymerase II preferentially associated with the smallest clutches while linker histone H1 and heterochromatin were enriched in the largest ones. Our results reveal how the chromatin fiber is formed at nanoscale level and link chromatin fiber architecture to stem cell state. [Display omitted] [Display omitted] •Nucleosomes are arranged in heterogeneous clutches along the chromatin fiber•The median number of nucleosomes per clutch in a given nucleus is cell-specific•Larger and denser clutches form the “closed” heterochromatin•Nucleosome-depleted regions separate nucleosome clutches Nucleosomes associate in discrete clutches along the chromatin fiber and clutch size correlates with cell pluripotency.
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2015.01.054