HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 53, 56024-56031, December 31, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/53/56024    most recent M411406200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tanaka, S. Articles by Bou-Gharios, G. Search for Related Content PubMed PubMed Citation Articles by Tanaka, S. Articles by Bou-Gharios, G. Social Bookmarking                      What's this?

Cooperativity between Far Upstream Enhancer and Proximal Promoter Elements of the Human 2(I) Collagen (COL1A2) Gene Instructs Tissue Specificity in Transgenic Mice^*

Shizuko Tanaka, Taras T. Antoniv, Ke Liu¶, Lu Wang, Dominic J. Wells¶, Francesco Ramirez||, and George Bou-Gharios**

From the Laboratory of Genetics and Organogenesis, Research Division of the Hospital for Special Surgery, and Department of Physiology and Biophysics, Weill Medical College of Cornell University, New York, New York 10021, the ^¶Gene Targeting Unit, Division of Neuroscience and Psychological Medicine, Imperial College School of Medicine, Charing Cross Hospital, London W6 8RP, United Kingdom, and the ^**Renal Medicine Division, Imperial College School of Medicine, Hammersmith Campus, London W12 ONN, United Kingdom

Interaction between the proximal (-378) promoter and the far upstream (-20 kb) enhancer is essential for tissue-specific expression of the human 2(I) collagen gene (COL1A2) in transgenic mice. Previous in vitro studies have shown that three Sp1 binding sites (around -300) are part of a cytokine-responsive element and that two TC-rich boxes (around -160 and -125) and a CBF/NFY consensus sequence (around -80) confer optimal promoter activity by interacting among themselves and with the upstream Sp1 sites. Here we report that mutations of the Sp1 binding sites, TC-rich boxes or CBF/NFY consensus sequence lead to reduced transgene activity, thus underscoring the functional interdependence of the proximal promoter elements. Loss of the Sp1 binding sites was associated with loss of transgene expression in osteoblasts, whereas elimination of the CBF/NFY binding site (alone or in combination with the TC-rich boxes) was correlated with a lack of activity in the ventral fascia and head dermis and musculature. Additionally, transgene expression in skin fascia fibroblasts depended on the integrity of the Sp1 binding sites and TC-rich boxes, and on their physical configuration. Evidence is also presented suggesting cooperativity between cis-acting elements of the far upstream enhancer and proximal promoter in assembling tissue-specific protein complexes. This study thus reiterates the complex and highly combinatorial nature of the regulatory network governing COL1A2 transcription in vivo.

Received for publication, October 6, 2004 , and in revised form, October 28, 2004.

^* This work was supported by Grant AR386481 from the National Institutes of Health, the St. Giles Foundation, the James D. Farley Family, and by the Medical Research Council. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Both authors contributed equally to this work.

^|| To whom correspondence should be addressed: Laboratory of Genetics and Organogenesis, Hospital for Special Surgery, 535 East 70th St., New York, NY 10021. Tel.: 212-774-7554; Fax: 212-774-7864; E-mail: ramirezf{at}hss.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. Ponticos, C. Harvey, T. Ikeda, D. Abraham, and G. Bou-Gharios JunB mediates enhancer/promoter activity of COL1A2 following TGF-{beta} induction Nucleic Acids Res., June 26, 2009; (2009) gkp544v1. [Abstract] [Full Text] [PDF]

				Y. Asano, M. Markiewicz, M. Kubo, G. Szalai, D. K. Watson, and M. Trojanowska Transcription Factor Fli1 Regulates Collagen Fibrillogenesis in Mouse Skin Mol. Cell. Biol., January 15, 2009; 29(2): 425 - 434. [Abstract] [Full Text] [PDF]

				N. Matsuo, S. Tanaka, M. K. Gordon, M. Koch, H. Yoshioka, and F. Ramirez CREB-AP1 Protein Complexes Regulate Transcription of the Collagen XXIV Gene (Col24a1) in Osteoblasts J. Biol. Chem., March 3, 2006; 281(9): 5445 - 5452. [Abstract] [Full Text] [PDF]

				T. T. Antoniv, S. Tanaka, B. Sudan, S. De Val, K. Liu, L. Wang, D. J. Wells, G. Bou-Gharios, and F. Ramirez Identification of a Repressor in the First Intron of the Human {alpha}2(I) Collagen Gene (COL1A2) J. Biol. Chem., October 21, 2005; 280(42): 35417 - 35423. [Abstract] [Full Text] [PDF]