Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow Print PDF (345K) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (25)
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Park, G. T.
Right arrow Articles by Morasso, M. I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Park, G. T.
Right arrow Articles by Morasso, M. I.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Nucleic Acids Research, 2002, Vol. 30, No. 2 515-522
© 2002 Oxford University Press

Bone morphogenetic protein-2 (BMP-2) transactivates Dlx3 through Smad1 and Smad4: alternative mode for Dlx3 induction in mouse keratinocytes

Geon Tae Park and Maria I. Morasso*

Developmental Skin Biology Unit, NIAMS, National Institutes of Health, Bethesda, MD 20892, USA

Expression of the Dlx3 homeodomain gene is induced in terminally differentiated epidermal cells. Dlx3 regulates gene expression in skin and plays important roles in patterning of the embryonic ectoderm through differential sensitivity to bone morphogenetic protein (BMP) signaling. We analyzed the expression of BMP family members in murine keratinocytes; BMP-2 is expressed in proliferative basal and differentiated suprabasal keratinocytes. BMP-2 induced transcription of Dlx3 within 12 h of treatment of keratinocytes cultured in vitro. We proceeded to delineate the BMP-2-responsive region to an area between –1917 and –1747 in the Dlx3 promoter. Gel shift assays with recombinant Smad1 and Smad4 demonstrated that this DNA fragment (–1917 to –1747) was competent in the formation of protein–DNA complexes. By deletion and mutational analyses we localized a Smad1/Smad4-binding site containing a GCAT motif, which showed similarity to other TGF-ß family responsive elements. Supershift assays with keratinocyte nuclear extracts and antibodies against members of the Smad family showed that this motif was able to form a complex with Smad1. Mutation of the Smad1/Smad4-binding site inhibited transcriptional activation of the Dlx3 gene by BMP-2. In the hair follicle, where Dlx3 is expressed in the hair matrix cells, BMP-2 also activates Dlx3 transcription. These results provide a possible mechanism of action for the BMP signaling pathway on the regulation of Dlx3.

* To whom correspondence should be addressed. Tel: +1 301 402 2888; Fax: +1 301 402 3417; Email: morasso{at}nih.gov


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
K. A. Berghorn, P. A. Clark-Campbell, L. Han, M. McGrattan, R. S. Weiss, and M. S. Roberson
Smad6 Represses Dlx3 Transcriptional Activity through Inhibition of DNA Binding
J. Biol. Chem., July 21, 2006; 281(29): 20357 - 20367.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
T. Oren, I. Torregroza, and T. Evans
An Oct-1 binding site mediates activation of the gata2 promoter by BMP signaling
Nucleic Acids Res., August 1, 2005; 33(13): 4357 - 4367.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
M. Q. Hassan, A. Javed, M. I. Morasso, J. Karlin, M. Montecino, A. J. van Wijnen, G. S. Stein, J. L. Stein, and J. B. Lian
Dlx3 Transcriptional Regulation of Osteoblast Differentiation: Temporal Recruitment of Msx2, Dlx3, and Dlx5 Homeodomain Proteins to Chromatin of the Osteocalcin Gene
Mol. Cell. Biol., October 15, 2004; 24(20): 9248 - 9261.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
S. M. Brugger, A. E. Merrill, J. Torres-Vazquez, N. Wu, M.-C. Ting, J. Y.-M. Cho, S. L. Dobias, S. E. Yi, K. Lyons, J. R. Bell, et al.
A phylogenetically conserved cis-regulatory module in the Msx2 promoter is sufficient for BMP-dependent transcription in murine and Drosophila embryos
Development, October 15, 2004; 131(20): 5153 - 5165.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. M. Hussein, E. K. Duff, and C. Sirard
Smad4 and {beta}-Catenin Co-activators Functionally Interact with Lymphoid-enhancing Factor to Regulate Graded Expression of Msx2
J. Biol. Chem., December 5, 2003; 278(49): 48805 - 48814.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
H. Benchabane and J. L. Wrana
GATA- and Smad1-Dependent Enhancers in the Smad7 Gene Differentially Interpret Bone Morphogenetic Protein Concentrations
Mol. Cell. Biol., September 15, 2003; 23(18): 6646 - 6661.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
S. Ruiz, C. Segrelles, A. Bravo, M. Santos, P. Perez, H. Leis, J. L. Jorcano, and J. M. Paramio
Abnormal epidermal differentiation and impaired epithelial-mesenchymal tissue interactions in mice lacking the retinoblastoma relatives p107 and p130
Development, June 1, 2003; 130(11): 2341 - 2353.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.