Sequence-dependent DNA condensation as a driving force of DNA phase separation

Nucleic Acids Research
Hyunju KangHajin Kim

Abstract

The physical properties of DNA have been suggested to play a central role in spatio-temporal organization of eukaryotic chromosomes. Experimental correlations have been established between the local nucleotide content of DNA and the frequency of inter- and intra-chromosomal contacts but the underlying physical mechanism remains unknown. Here, we combine fluorescence resonance energy transfer (FRET) measurements, precipitation assays, and molecular dynamics simulations to characterize the effect of DNA nucleotide content, sequence, and methylation on inter-DNA association and its correlation with DNA looping. First, we show that the strength of DNA condensation mediated by poly-lysine peptides as a reduced model of histone tails depends on the DNA's global nucleotide content but also on the local nucleotide sequence, which turns out to be qualitatively same as the condensation by spermine. Next, we show that the presence and spatial arrangement of C5 methyl groups determines the strength of inter-DNA attraction, partially explaining why RNA resists condensation. Interestingly, multi-color single molecule FRET measurements reveal strong anti-correlation between DNA looping and DNA-DNA association, suggesting that a common biophys...Continue Reading

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Citations

Feb 7, 2019·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Benjamin CroopKyu Young Han
Jun 5, 2019·Nature Communications·Mi-Sun KangKyungjae Myung
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Jun 17, 2020·Nucleic Acids Research·Amit SrivastavaXiangyun Qiu
May 21, 2019·Nucleic Acids Research·Tiedong SunLars Nordenskiöld
Aug 29, 2020·Nature Communications·Byeong-Kwon SohnHajin Kim
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Feb 15, 2021·Biophysical Journal·John T King, Anisha Shakya
Mar 1, 2021·Biophysical Journal·Fernando MuzzopappaFabian Erdel
Mar 31, 2021·Nucleic Acids Research·Luca BarberiMartin Lenz
Aug 6, 2021·Archives of Biochemistry and Biophysics·Zhaoqian SuYinghao Wu
Apr 25, 2020·Journal of the American Chemical Society·Ya-Jun YangXing-Hua Zhang
Sep 8, 2021·Nature Communications·Yunhui PengAnna R Panchenko

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Methods Mentioned

BETA
chemical modifications
X-ray
FRET
PCR

Software Mentioned

LINCS
AMBER
Gromacs
SETTLE

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