Fractal Characterization of Chromatin Decompaction in Live Cells

Chromatin organization has a fundamental impact on the whole spectrum of genomic functions. Quantitative characterization of the chromatin structure, particularly at submicron length scales where chromatin fractal globules are formed, is critical to understanding this structure-function relationship...

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Bibliographic Details
Published in:Biophysical journal 2015-12, Vol.109 (11), p.2218-2226
Main Authors: Yi, Ji, Stypula-Cyrus, Yolanda, Blaha, Catherine S., Roy, Hemant K., Backman, Vadim
Format: Article
Language:English
Subjects:
Cell Biophysics
Cell Survival
Cells
Chromatin
Chromatin - chemistry
Chromatin - drug effects
Chromatin - metabolism
Diffraction
Fractals
Genomics
Histone Deacetylase Inhibitors - pharmacology
HT29 Cells
Humans
Microscopy
Tomography, Optical
Valproic Acid - pharmacology
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Summary:Chromatin organization has a fundamental impact on the whole spectrum of genomic functions. Quantitative characterization of the chromatin structure, particularly at submicron length scales where chromatin fractal globules are formed, is critical to understanding this structure-function relationship. Such analysis is currently challenging due to the diffraction-limited resolution of conventional light microscopy. We herein present an optical approach termed inverse spectroscopic optical coherence tomography to characterize the mass density fractality of chromatin, and we apply the technique to observe chromatin decompaction in live cells. The technique makes it possible for the first time, to our knowledge, to sense intracellular morphology with length-scale sensitivity from ∼30 to 450 nm, thus primarily probing the higher-order chromatin structure, without resolving the actual structures. We used chromatin decompaction due to inhibition of histone deacytelases and measured the subsequent changes in the fractal dimension of the intracellular structure. The results were confirmed by transmission electron microscopy and confocal fluorescence microscopy.
ISSN:0006-3495
1542-0086
DOI:10.1016/j.bpj.2015.10.014