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Open Access Research

An in vitro-identified high-affinity nucleosome-positioning signal is capable of transiently positioning a nucleosome in vivo

Lia E Gracey1, Zhi-Ying Chen2, Jay M Maniar1, Anton Valouev3, Arend Sidow13, Mark A Kay12* and Andrew Z Fire13*

Author Affiliations

1 Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA

2 Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA

3 Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA

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Epigenetics & Chromatin 2010, 3:13  doi:10.1186/1756-8935-3-13

Published: 1 July 2010

Abstract

Background

The physiological function of eukaryotic DNA occurs in the context of nucleosomal arrays that can expose or obscure defined segments of the genome. Certain DNA sequences are capable of strongly positioning a nucleosome in vitro, suggesting the possibility that favorable intrinsic signals might reproducibly structure chromatin segments. As high-throughput sequencing analyses of nucleosome coverage in vitro and in vivo have become possible, a vigorous debate has arisen over the degree to which intrinsic DNA:nucleosome affinities orchestrate the in vivo positions of nucleosomes, thereby controlling physical accessibility of specific sequences in DNA.

Results

We describe here the in vivo consequences of placing a synthetic high-affinity nucleosome-positioning signal, the 601 sequence, into a DNA plasmid vector in mice. Strikingly, the 601 sequence was sufficient to position nucleosomes during an early phase after introduction of the DNA into the mice (when the plasmid vector transgene was active). This positioning capability was transient, with a loss of strong positioning at a later time point when the transgenes had become silent.

Conclusions

These results demonstrate an ability of DNA sequences selected solely for nucleosome affinity to organize chromatin in vivo, and the ability of other mechanisms to overcome these interactions in a dynamic nuclear environment.