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Molecular and Cellular Biology, August 2006, p. 5850-5860, Vol. 26, No. 15
0270-7306/06/$08.00+0     doi:10.1128/MCB.01854-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

A Distant Upstream Locus Control Region Is Critical for Expression of the Kit Receptor Gene in Mast Cells

Georgina Berrozpe,1 Valter Agosti,1 Christine Tucker,1 Cedric Blanpain,3 Katia Manova,2 and Peter Besmer1,4,5*

Developmental Biology Program,1 Molecular Cytology Facility, Sloan-Kettering Institute,2 Howard Hughes Medical Institute, The Rockefeller University,3 Gerstner Sloan-Kettering Graduate School of Biomedical Sciences,4 Weill Graduate School of Medical Sciences, Cornell University, New York, New York 100215

Received 21 September 2005/ Returned for modification 25 November 2005/ Accepted 7 May 2006

The Kit receptor tyrosine kinase functions in hematopoiesis, melanogenesis, and gametogenesis and in interstitial cells of Cajal. We previously identified two upstream hypersensitive site (HS) clusters in mast cells and melanocytes. Here we investigated the roles of these 5' HS sequences in Kit expression using transgenic mice carrying Kit-GFP reporter constructs. In these mice there is close correspondence between Kit-GFP reporter and endogenous Kit gene expression in most tissues analyzed. Deletion analysis defined the 5' upstream HS cluster region as critical for Kit expression in mast cells. Furthermore, chromatin immunoprecipitation analysis in mast cells showed that H3 and H4 histone hyperacetylation and RNA polymerase II recruitment within the Kit promoter and in the 5' HS region were associated with Kit expression. Therefore, the 5' upstream hypersensitivity sites appear to be critical components of locus control region-mediated Kit gene activation in mast cells.

* Corresponding author. Mailing address: Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021. Phone: (212) 639-8188. Fax: (212) 717-3623. E-mail: p-besmer{at}ski.mskcc.org.

Molecular and Cellular Biology, August 2006, p. 5850-5860, Vol. 26, No. 15
0270-7306/06/$08.00+0     doi:10.1128/MCB.01854-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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