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DNA compaction by the higher-order assembly of PRH/Hex homeodomain protein oligomers

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Soufi, Abdenour, Sawasdichai, Anyaporn, Shukla, Anshuman, Noy, Peter, Dafforn, Tim, Smith, Corinne, Jayaraman, Padma-Sheela and Gaston, Kevin. (2010) DNA compaction by the higher-order assembly of PRH/Hex homeodomain protein oligomers. Nucleic Acids Research, Vol.38 (No.21). pp. 7513-7525. ISSN 0305-1048

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Official URL: http://dx.doi.org/10.1093/nar/gkq659

Abstract

Protein self-organization is essential for the establishment and maintenance of nuclear architecture and for the regulation of gene expression. We have shown previously that the Proline-Rich Homeodomain protein (PRH/Hex) self-assembles to form oligomeric complexes that bind to arrays of PRH binding sites with high affinity and specificity. We have also shown that many PRH target genes contain suitably spaced arrays of PRH sites that allow this protein to bind and regulate transcription. Here, we use analytical ultracentrifugation and electron microscopy to further characterize PRH oligomers. We use the same techniques to show that PRH oligomers bound to long DNA fragments self-associate to form highly ordered assemblies. Electron microscopy and linear dichroism reveal that PRH oligomers can form protein–DNA fibres and that PRH is able to compact DNA in the absence of other proteins. Finally, we show that DNA compaction is not sufficient for the repression of PRH target genes in cells. We conclude that DNA compaction is a consequence of the binding of large PRH oligomers to arrays of binding sites and that PRH is functionally and structurally related to the Lrp/AsnC family of proteins from bacteria and archaea, a group of proteins formerly thought to be without eukaryotic equivalents.

Item Type:	Journal Article
Subjects:	Q Science > QH Natural history
Divisions:	Faculty of Science > Life Sciences (2010- ) > Biological Sciences ( -2010)
Library of Congress Subject Headings (LCSH):	DNA-binding proteins, Transcription factors, Gene expression
Journal or Publication Title:	Nucleic Acids Research
Publisher:	Oxford University Press
ISSN:	0305-1048
Date:	31 July 2010
Volume:	Vol.38
Number:	No.21
Page Range:	pp. 7513-7525
Identification Number:	10.1093/nar/gkq659
Status:	Peer Reviewed
Access rights to Published version:	Open Access
Funder:	Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), Wellcome Trust (London, England)
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URI:	http://wrap.warwick.ac.uk/id/eprint/3853