X-Ray Scattering Studies of Human Genome Organization
The hierarchical organization of the chromatin fiber, the functional form of DNA in cells, has been extensively studied from a single nucleosome to the genome-wide scale [1,2]. Chromosome conformation capture techniques revealed a detailed static picture of the genome's 3D folded state inside the cell nucleus, revealing presence of loops, topologically associated domains, A/B compartments and chromosome territories [3–5]. However, the complementary microscopy study that is necessary to bridge the interaction frequency and physical distance for the complete 3D picture of genome organization is limited by the wavelength of visible light.
We study the organization of chromatin by using small angle X-ray scattering (SAXS) technique, which captures the structural information from a few to several hundred nanometers [6]. SAXS is a powerful tool to study the structure of biomacromolecules [7], using a high-flux X-ray light with a wavelength of angstroms to be scattered by electrons in a sample. It allows us to obtain a spatial distribution of electrons and thus, 3D structure of the sample. By utilizing SAXS, we study the chromatin structure and the 3D organization of the human genome as well as the physical principles behind its folding.
1. Alberts et. al., Molecular Biology of the Cell (2002)
2. Van Holde, K. E., Chromatin (2012)
3. Gibcus & Dekker, Mol. Cell 49, 773–782 (2013)
4. Dekker et. al., Nat. Rev. Genet. 14, 390–403 (2013)
5. Bonev & Cavalli, Nat. Rev. Genet. 17, 661–678 (2016)
6. Glatter et. al., Small Angle X-ray Scattering (1982)
7. Koch et. al., Q. Rev. Biophys., 36 (2003)
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