Chromatin Structure Can Strongly Facilitate Enhancer Action over a Distance
Numerous DNA transactions in eukaryotic nuclei are regulated by elements (enhancers) that can directly interact with their targets over large regions of DNA organized into chromatin. The mechanisms allowing communication over a distance in chromatin are unknown. We have established an experimental s...
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Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 103; no. 47; pp. 17690 - 17695 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
United States
National Academy of Sciences
21.11.2006
National Acad Sciences |
Subjects | |
Online Access | Get full text |
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Summary: | Numerous DNA transactions in eukaryotic nuclei are regulated by elements (enhancers) that can directly interact with their targets over large regions of DNA organized into chromatin. The mechanisms allowing communication over a distance in chromatin are unknown. We have established an experimental system allowing quantitative analysis of the impact of chromatin structure on distant transcriptional regulation. Assembly of relaxed or linear DNA templates into subsaturated chromatin results in a strong increase of the efficiency of distant enhancer-promoter E-P communication and activation of transcription. The effect is directly proportional to the efficiency of chromatin assembly and cannot be explained only by DNA compaction. Transcription activation on chromatin templates is enhancer- and activator-dependent, and must be accompanied by direct E-P interaction and formation of a chromatin loop. Previously we have shown that DNA supercoiling can strongly facilitate E-P communication on histone-free DNA. The effects of chromatin assembly and DNA supercoiling on the communication are quantitatively similar, but the efficiency of enhancer action in subsaturated chromatin does not depend on the level of unconstrained DNA supercoiling. Thus chromatin structure per se can support highly efficient communication over a distance and functionally mimic the supercoiled state characteristic for prokaryotic DNA. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by Gary Felsenfeld, National Institutes of Health, Bethesda, MD, and approved September 28, 2006 Present address: Department of Biochemistry, University of Medicine and Dentistry of New Jersey, Piscataway, NJ 08854. Author contributions: M.A.R. and Y.S.P. contributed equally to this work; V.M.S. designed research; M.A.R., Y.S.P., and Y.-H.W. performed research; M.A.R., Y.S.P., V.A.B., Y.-H.W., and V.M.S. contributed new reagents/analytic tools; M.A.R., Y.S.P., V.A.B., and V.M.S. analyzed data; and V.M.S. wrote the paper. |
ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.0603819103 |