ArticleNucleic acids research2006
The human vitamin D-binding protein gene contains locus control determinants sufficient for autonomous activation in hepatic chromatin.
Article in Nucleic acids research, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- The alpha-fetoprotein enhancer region activates the albumin and alpha-fetoprotein promoters during liver development.Developmental biology · 2009Article
- 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.Molecular and cellular biology · 2007Article
- Common variants of the vitamin D binding protein gene and adverse health outcomes.Critical reviews in clinical laboratory sciencesReview
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Authors and funding
4 authors.
Funding
Abstract
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.
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