This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
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 arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kaufman, C. K.
Right arrow Articles by Fuchs, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kaufman, C. K.
Right arrow Articles by Fuchs, E.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, June 2002, p. 4293-4308, Vol. 22, No. 12
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.12.4293-4308.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Dissection of a Complex Enhancer Element: Maintenance of Keratinocyte Specificity but Loss of Differentiation Specificity

Charles K. Kaufman,1,{dagger} Satrajit Sinha,1,{ddagger} Diana Bolotin,1,{dagger} Jie Fan,1 and Elaine Fuchs1,2*

Department of Molecular Genetics and Cell Biology, Howard Hughes Medical Institute, The University of Chicago, Chicago, Illinois 60637,,1 Laboratory of Mammalian Cell Biology and Development, Howard Hughes Medical Institute, Rockefeller University, New York, New York 100212

Received 30 August 2001/ Returned for modification 11 October 2001/ Accepted 20 March 2002

In this report, we explored the mechanisms underlying keratinocyte-specific and differentiation-specific gene expression in the skin. We have identified five keratinocyte-specific, open chromatin regions that exist within the 6 kb of 5' upstream regulatory sequence known to faithfully recapitulate the strong endogenous keratin 5 (K5) promoter and/or enhancer activity. One of these, DNase I-hypersensitive site (HSs) 4, was unique in that it acted independently to drive abundant and keratinocyte-specific reporter gene activity in culture and in transgenic mice, despite the fact that it was not essential for K5 enhancer activity. We have identified evolutionarily conserved regulatory elements and a number of their associated proteins that bind to this compact and complex enhancer element. The 125-bp 3' half of this element (referred to as 4.2) is by far the smallest known strong enhancer element possessing keratinocyte-specific activity in vivo. Interestingly, its activity is restricted to a subset of progeny of K5-expressing cells located within the sebaceous gland. The other half of HSs 4 (termed 4.1) possesses activity to suppress sebocyte-specific expression and induce expression in the channel (inner root sheath) cells surrounding the hair shaft. Our findings lead us to a view of keratinocyte gene expression which is determined by multiple regulatory modules, many of which contain AP-2 and/or Sp1/Sp3 binding sites for enhancing expression in skin epithelium, but which also harbor one or more unique sites for the binding of factors which determine specificity. Through mixing and matching of these modules, additional levels of specificity are obtained, indicating that both transcriptional repressors and activators govern the specificity.

* Corresponding author. Mailing address: Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, Rockefeller University, Rockefeller Research Bldg., Rm. 1250, 1230 York Ave., New York, NY 10021-6399. Fax: (212) 327-7935. E-mail: fuchs{at}rockvax.rockefeller.edu.

{dagger} Present address: Laboratory of Mammalian Cell Biology, Howard Hughes Medical Institute, Rockefeller University, New York, NY 10021.

{ddagger} Department of Biochemistry, State University of New York at Buffalo, Buffalo, N.Y.

Molecular and Cellular Biology, June 2002, p. 4293-4308, Vol. 22, No. 12
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.12.4293-4308.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Pujal, J., Huch, M., Jose, A., Abasolo, I., Rodolosse, A., Duch, A., Sanchez-Palazon, L., Smith, F. J. D., McLean, W. H. I., Fillat, C., Real, F. X. (2009). Keratin 7 promoter selectively targets transgene expression to normal and neoplastic pancreatic ductal cells in vitro and in vivo. FASEB J. 23: 1366-1375 [Abstract] [Full Text]  
  • Antonini, D., Rossi, B., Han, R., Minichiello, A., Di Palma, T., Corrado, M., Banfi, S., Zannini, M., Brissette, J. L., Missero, C. (2006). An Autoregulatory Loop Directs the Tissue-Specific Expression of p63 through a Long-Range Evolutionarily Conserved Enhancer. Mol. Cell. Biol. 26: 3308-3318 [Abstract] [Full Text]  
  • Liu, F., Pore, N., Kim, M., Voong, K. R., Dowling, M., Maity, A., Kao, G. D. (2006). Regulation of Histone Deacetylase 4 Expression by the SP Family of Transcription Factors. Mol. Biol. Cell 17: 585-597 [Abstract] [Full Text]  
  • Wang, X., Bolotin, D., Chu, D. H., Polak, L., Williams, T., Fuchs, E. (2006). AP-2{alpha}: a regulator of EGF receptor signaling and proliferation in skin epidermis. JCB 172: 409-421 [Abstract] [Full Text]  
  • Tao, J., Kuliyev, E., Wang, X., Li, X., Wilanowski, T., Jane, S. M., Mead, P. E., Cunningham, J. M. (2005). BMP4-dependent expression of Xenopus Grainyhead-like 1 is essential for epidermal differentiation. Development 132: 1021-1034 [Abstract] [Full Text]  
  • Ruiz, S., Segrelles, C., Bravo, A., Santos, M., Perez, P., Leis, H., Jorcano, J. L., Paramio, J. M. (2003). Abnormal epidermal differentiation and impaired epithelial-mesenchymal tissue interactions in mice lacking the retinoblastoma relatives p107 and p130. Development 130: 2341-2353 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»