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

Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland 21201 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 ca...

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Published in:American journal of physiology. Lung cellular and molecular physiology 2003-01, Vol.284 (1), p.160-L168
Main Authors: Lee, Insong James, Hyun, Sang Won, Nandi, Asit, Kim, K. Chul
Format: Article
Language:English
Subjects:
Amino Acid Sequence - genetics
Animals
Base Sequence - genetics
Binding Sites
Cricetinae
Erythroid-Specific DNA-Binding Factors
Gene Expression Regulation - physiology
Genes, Regulator - physiology
Humans
Mucin-1 - genetics
Promoter Regions, Genetic - genetics
Transcription Factors - metabolism
Transcription, Genetic - physiology
Tumor Cells, Cultured
YY1 Transcription Factor
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Summary:Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland 21201 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 , we cloned a 2.4-kb fragment containing the promoter region of the hamster Muc1 gene and analyzed it for its ability to mediate transcription. Transcriptional initiation was localized to 22   base pairs downstream of the TATA box. We performed functional analysis of the Muc1 promoter in hamster (HP-1 and Chinese hamster ovary) 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 element (P-NRE) between nucleotides 1,652 and 1,614 were found to be active in transfected cells. The P-NRE contains a yin yang 1 (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 suggest that YY1 may play an inhibitory role in the transcription of the Muc1 gene. promoter; expression; negative regulatory region; protein binding; yin yang 1
ISSN:1040-0605
1522-1504
DOI:10.1152/ajplung.00342.2000