TY - JOUR
T1 - Rapid spontaneous accessibility of nucleosomal DNA
AU - Li, Gu
AU - Levitus, Marcia
AU - Bustamante, Carlos
AU - Widom, Jonathan
N1 - Funding Information:
We are grateful to S. Huang for valuable discussions and comments on the manuscript. We thank J. Little for the LexA expression plasmid, and the Keck Biophysics Facility at Northwestern University for the use of instruments. This work was supported by US National Institutes of Health (NIH) grants GM54692 and GM58617 to J.W., and by NIH grant GM32543, and US Department of Energy grants DE-AC03-76DF00098, GTL2BN Microscopies of Molecular Machines, and SNANOB Design of Autonomous Nanobots to C.B.
PY - 2005/1
Y1 - 2005/1
N2 - DNA wrapped in nucleosomes is sterically occluded, creating obstacles for proteins that must bind it. How proteins gain access to DNA buried inside nucleosomes is not known. Here we report measurements of the rates of spontaneous nucleosome conformational changes in which a stretch of DNA transiently unwraps off the histone surface, starting from one end of the nucleosome, and then rewraps. The rates are rapid. Nucleosomal DNA remains fully wrapped for only ∼250 ms before spontaneously unwrapping; unwrapped DNA rewraps within 10-50 ms. Spontaneous unwrapping of nucleosomal DNA allows any protein rapid access even to buried stretches of the DNA. Our results explain how remodeling factors can be recruited to particular nucleosomes on a biologically relevant timescale, and they imply that the major impediment to entry of RNA polymerase into a nucleosome is rewrapping of nucleosomal DNA, not unwrapping.
AB - DNA wrapped in nucleosomes is sterically occluded, creating obstacles for proteins that must bind it. How proteins gain access to DNA buried inside nucleosomes is not known. Here we report measurements of the rates of spontaneous nucleosome conformational changes in which a stretch of DNA transiently unwraps off the histone surface, starting from one end of the nucleosome, and then rewraps. The rates are rapid. Nucleosomal DNA remains fully wrapped for only ∼250 ms before spontaneously unwrapping; unwrapped DNA rewraps within 10-50 ms. Spontaneous unwrapping of nucleosomal DNA allows any protein rapid access even to buried stretches of the DNA. Our results explain how remodeling factors can be recruited to particular nucleosomes on a biologically relevant timescale, and they imply that the major impediment to entry of RNA polymerase into a nucleosome is rewrapping of nucleosomal DNA, not unwrapping.
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U2 - 10.1038/nsmb869
DO - 10.1038/nsmb869
M3 - Article
C2 - 15580276
AN - SCOPUS:11444262202
SN - 1545-9993
VL - 12
SP - 46
EP - 53
JO - Nature Structural and Molecular Biology
JF - Nature Structural and Molecular Biology
IS - 1
ER -