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Nucleic Acids Research 2006 34(8):2154-2165; doi:10.1093/nar/gkl174
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Published online 28 April 2006

© The Author 2006. Published by Oxford University Press. All rights reserved
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

Article

The human vitamin D-binding protein gene contains locus control determinants sufficient for autonomous activation in hepatic chromatin

Tomoko Hiroki, Young-Han Song, Stephen A. Liebhaber and Nancy E. Cooke*

Departments of Medicine and Genetics, University of Pennsylvania Philadelphia, PA 19104, USA

*To whom correspondence should be addressed at 752b Clinical Research Building, University of Pennsylvania, 415 Curie Boulevard, Philadelphia, PA 19104, USA. Tel: +1 215 898 4425; Fax: +1 215 573 5809; Email: necooke{at}mail.med.upenn.edu

Received February 1, 2006. Revised March 8, 2006. Accepted March 20, 2006.

The human vitamin D-binding protein (hDBP) gene is a member of a cluster that includes albumin, {alpha}-fetoprotein and {alpha}-albumin genes. The common origin, physical linkage and hepatic expression of these four genes predict shared regulatory element(s). However, separation of hDBP from the other three genes by 1.5 Mb argues that hDBP may be under autonomous control. To test for hDBP autonomy, mouse lines were generated with a transgene containing the hDBP gene along with extensive flanking sequences. Expression of this transgene was hepatic, robust and proportional to transgene copy number. DNase I hypersensitive site (HS) mapping revealed five liver-specific HS at the hDBP locus: HSI and HSIII at –2.1 kb and –0.13 kb upstream of the transcription initiation site, HSIV and HSV within intron 1 and HSVII located 3' to the poly(A) site. A second transgene with minimal flanking sequences confirmed the sufficiency of these gene-proximal determinants for hepatic activation. The hepatic-specific HS aligned with segments of phylogenetically conserved non-coding sequences. These data demonstrate the autonomy of the hDBP locus and suggest that this control is mediated by chromatin-based locus control determinants in close proximity to, and within the transcription unit.

Present address: Young-Han Song, Ilsong Institute of Life Science, Hallym University, Anyang 431-060, Korea


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Home page
 Mol. Cell. Biol.Home page
T. Hiroki, S. A. Liebhaber, and N. E. Cooke
An Intronic Locus Control Region Plays an Essential Role in the Establishment of an Autonomous Hepatic Chromatin Domain for the Human Vitamin D-Binding Protein Gene
Mol. Cell. Biol., November 1, 2007; 27(21): 7365 - 7380.
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