TY - JOUR
T1 - Sequence-dependent DNA condensation as a driving force of DNA phase separation
AU - Kang, Hyunju
AU - Yoo, Jejoong
AU - Sohn, Byeong Kwon
AU - Lee, Seung Won
AU - Lee, Hong Soo
AU - Ma, Wenjie
AU - Kee, Jung Min
AU - Aksimentiev, Aleksei
AU - Kim, Hajin
N1 - Funding Information:
J.Y. and A.A. gladly acknowledge supercomputer time provided through XSEDE Allocation Grant [MCA05S028] and the Blue Waters Sustained Petascale Computer System (UIUC). We thank Dr Min Ju Shon for helpful discussions. National Research Foundation of Korea [2017R1D1A1B0 3036239, 2017M3A9E2062181, 2015R1C1A1A02036405]; Institute for Basic Science [IBS-R022-D1, IBS-R007-Y1]; National Science Foundation (USA) [PHY-1430124 to J.Y. and A.A.]; National Institutes of Health [P41 GM104601]. Funding for open access charge: National Research Foundation of Korea.
Funding Information:
National Research Foundation of Korea [2017R1D1A1B0 3036239, 2017M3A9E2062181, 2015R1C1A1A02036405]; Institute for Basic Science [IBS-R022-D1, IBS-R007-Y1]; National Science Foundation (USA) [PHY-1430124 to J.Y. and A.A.]; National Institutes of Health [P41 GM104601]. Funding for open access charge: National Research Foundation of Korea. Conflict of interest statement. None declared.
Publisher Copyright:
© The Author(s) 2018.
PY - 2018/10/12
Y1 - 2018/10/12
N2 - 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 polylysine 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, multicolor single molecule FRET measurements reveal strong anti-correlation between DNA looping and DNA–DNA association, suggesting that a common biophysical mechanism underlies them. We propose that the differential affinity between DNA regions of varying sequence pattern may drive the phase separation of chromatin into chromosomal subdomains.
AB - 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 polylysine 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, multicolor single molecule FRET measurements reveal strong anti-correlation between DNA looping and DNA–DNA association, suggesting that a common biophysical mechanism underlies them. We propose that the differential affinity between DNA regions of varying sequence pattern may drive the phase separation of chromatin into chromosomal subdomains.
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U2 - 10.1093/nar/gky639
DO - 10.1093/nar/gky639
M3 - Article
C2 - 30032232
AN - SCOPUS:85054889592
SN - 0305-1048
VL - 46
SP - 9401
EP - 9413
JO - Nucleic acids research
JF - Nucleic acids research
IS - 18
ER -