Histone fold modifications control nucleosome unwrapping and disassembly
Nucleosomes are stable DNA–histone protein complexes that must be unwrapped and disassembled for genome expression, replication, and repair. Histone posttranslational modifications (PTMs) are major regulatory factors of these nucleosome structural changes, but the molecular mechanisms associated wit...
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Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 108; no. 31; pp. 12711 - 12716 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
National Academy of Sciences
02.08.2011
National Acad Sciences |
Subjects | |
Online Access | Get full text |
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Summary: | Nucleosomes are stable DNA–histone protein complexes that must be unwrapped and disassembled for genome expression, replication, and repair. Histone posttranslational modifications (PTMs) are major regulatory factors of these nucleosome structural changes, but the molecular mechanisms associated with PTM function remains poorly understood. Here we demonstrate that histone PTMs within distinct structured regions of the nucleosome directly regulate the inherent dynamic properties of the nucleosome. Precise PTMs were introduced into nucleosomes by chemical ligation. Single molecule magnetic tweezers measurements determined that only PTMs near the nucleosome dyad increase the rate of histone release in unwrapped nucleosomes. In contrast, FRET and restriction enzyme analysis reveal that only PTMs throughout the DNA entry–exit region increase unwrapping and enhance transcription factor binding to nucleosomal DNA. These results demonstrate that PTMs in separate structural regions of the nucleosome control distinct dynamic events, where the dyad regulates disassembly while the DNA entry–exit region regulates unwrapping. These studies are consistent with the conclusion that histone PTMs may independently influence nucleosome dynamics and associated chromatin functions. |
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Bibliography: | http://dx.doi.org/10.1073/pnas.1106264108 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1 Edited by Steven Henikoff, Fred Hutchinson Cancer Research Center, Seattle, WA, and approved June 14, 2011 (received for review April 19, 2011) Author contributions: J.J.O. and M.G.P. designed research; M.S., J.A.N., and M.Z. performed research; J.C.S., M.B.F., and M.M. contributed new reagents/analytic tools; M.S., J.A.N., and R.A.F. analyzed data; and M.S., J.A.N., R.F., J.J.O., and M.G.P. wrote the paper. |
ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.1106264108 |