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Am J Physiol Lung Cell Mol Physiol (September 27, 2002). doi:10.1152/ajplung.00342.2000
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Articles in PresS, published online ahead of print September 27, 2002
Am J Physiol Lung Cell Mol Physiol, 10.1152/ajplung.00342.2000
Submitted on September 27, 2000
Accepted on September 11, 2002

Transcriptional regulation of the hamster Muc1 gene: Identification of a putative negative regulatory element

Insong James Lee1, Sang Won Hyun1, Asit Nandi1, and K. Chul Kim1*

1 Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD, USA

* To whom correspondence should be addressed. E-mail: kkim{at}umaryland.edu.

The mucin gene, Muc1 is expressed in glandular epithelial cells and is involved in lubricative and protective functions. It is also overexpressed in many carcinomas including breast and lung cancer cells. To study the transcriptional regulation of Muc1, a 2.4 kb fragment containing the promoter region of the hamster Muc1 gene was cloned and analyzed for its ability to mediate transcription. Transcriptional initiation was localized to 22 base pairs downstream of the TATA box. Functional analysis of the Muc1 promoter was performed in hamster (HP-1 and CHO) and human cells (MCF-7, A549 and BEAS-2B) using deletion/reporter constructs. A positive regulatory region between bases -555 and -252 and a putative negative regulatory region (P-NRE) between nucleotides -1652 and -1614 were found to be active in transfected cells. The P-NRE contains a YY1 transcription factor binding site and electrophoretic mobility shift assays with HP-1 cell nuclear extract revealed the binding of YY1 to this site. Our data suggests that YY1 may play an inhibitory role in the transcription of the Muc1 gene.




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