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PMID: 17101994 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Chromatin structure can strongly facilitate enhancer action over a distance.

Rubtsov MA, Polikanov YS, Bondarenko VA, Wang YH, Studitsky VM

Abstract

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.

MeSH Terms
Animals Chromatin/chemistry DNA, Superhelical/chemistry Enhancer Elements, Genetic Gene Expression Regulation Nucleic Acid Conformation Nucleosomes/chemistry,metabolism Transcription, Genetic
Chemicals
Chromatin DNA, Superhelical Nucleosomes
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Rubtsov Mikhail A
Department of Pharmacology, University of Medicine and Dentistry of New Jersey, Piscataway, NJ 08854, USA.
Polikanov Yury S
Bondarenko Vladimir A
Wang Yuh-Hwa
Studitsky Vasily M
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
2006-11-21
Epub
2006-00-13
Pages
17690-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC1693808
Subset
IM
Grants
NIGMS NIH HHS · R01 GM058650 · United States
NIGMS NIH HHS · GM58650 · United States
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