Advertisement
JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/jbc.M003039200 on June 6, 2000

J. Biol. Chem., Vol. 275, Issue 37, 29031-29041, September 15, 2000
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
275/37/29031    most recent
M003039200v1
Right arrow Submit a Letter to Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Vorachek, W. R.
Right arrow Articles by Locker, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Vorachek, W. R.
Right arrow Articles by Locker, J.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Distant Enhancers Stimulate the Albumin Promoter through Complex Proximal Binding Sites*

William R. VorachekDagger §, Claire M. SteppanDagger , Michele Lima||, Heather BlackDagger , Raka BhattacharyaDagger **, Ping WenDagger Dagger Dagger , Yasuo KajiyamaDagger ||, and Joseph LockerDagger ||§§

From the Dagger  Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261 and the || Department of Pathology, Albert Einstein College of Medicine, Bronx, New York 10461

The albumin-alpha -fetoprotein locus epitomizes the main features of transcriptional regulation of fetal and adult hepatocyte-specific genes: developmentally regulated promoters and strong distant enhancers. Full enhancer activity required only a proximal albumin-promoter region containing the TATA box, hepatic nuclear factor 1 (HNF1), and nuclear factor Y (NF-Y) sites. Deletion of the HNF1 site abrogated enhancer and promoter activity, whereas methylation of the site reduced all activity by about 3-fold. Deletion of the NF-Y site attenuated activity by about half, but much of the activity could be replaced by juxtaposition of an upstream region (designated distal element IV). Gel shift and competition analysis demonstrated that binding of architectural factors overlapped NF-Y binding. Moreover, a mutation that eliminated NF-Y binding but only minimally perturbed the surrounding region did not affect enhancer function. In plasmids with a second promoter, the enhancers simultaneously stimulated both albumin and alpha -fetoprotein promoters with minimal competition, but surprisingly some mutations in the albumin promoter attenuated expression from both promoters, whereas another uncoupled their expression. With single promoters, the function of the proximal promoter region was controlled by three parameters in the following hierarchy: HNF1 binding > local architecture > NF-Y binding, but integrated two-promoter function had a much greater dependence on NF-Y.

* This work was supported by National Institutes of Health Grants CA68440 and CA76354 and American Cancer Society Grant NP-955.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ Present address: Dept. of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331.

Present address: Pfizer-Central Research, Box 943, Eastern Point Road, Groton, CT 06320.

** Present address: James A. Haley Research Center-151, 13000 Bruce. B. Downs Blvd., Tampa, FL 33612.

Dagger Dagger Present address: University Hospitals of Cleveland, Dept. of Pathology, 11000 Euclid Ave., Cleveland, OH 44106.

§§ To whom correspondence should be addressed: Albert Einstein College of Medicine, School of Medicine, Dept. of Pathology, Bronx, NY 10461. Tel.: 718-430-3422; Fax: 718-430-3483; E-mail: locker@aecom. yu.edu.

Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
Y. Kajiyama, J. Tian, and J. Locker
Characterization of Distant Enhancers and Promoters in the Albumin-{alpha}-Fetoprotein Locus during Active and Silenced Expression
J. Biol. Chem., October 6, 2006; 281(40): 30122 - 30131.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
T. Hiroki, Y.-H. Song, S. A. Liebhaber, and N. E. Cooke
The human vitamin D-binding protein gene contains locus control determinants sufficient for autonomous activation in hepatic chromatin.
Nucleic Acids Res., January 1, 2006; 34(8): 2154 - 2165.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
Y. Kajiyama, J. Tian, and J. Locker
Regulation of {alpha}-Fetoprotein Expression by Nkx2.8
Mol. Cell. Biol., September 1, 2002; 22(17): 6122 - 6130.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
J. Locker, D. Ghosh, P.-V. Luc, and J. Zheng
Definition and prediction of the full range of transcription factor binding sites--the hepatocyte nuclear factor 1 dimeric site
Nucleic Acids Res., September 1, 2002; 30(17): 3809 - 3817.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
S. Miccadei, R. De Leo, E. Zammarchi, P. G. Natali, and D. Civitareale
The Synergistic Activity of Thyroid Transcription Factor 1 and Pax 8 Relies on the Promoter/Enhancer Interplay
Mol. Endocrinol., April 1, 2002; 16(4): 837 - 846.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2000 by the American Society for Biochemistry and Molecular Biology.
Advertisement
spacer
Advertisement
Advertisement