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Nuclear factor 1-C2 contributes to the tissue-specific activation of a milk protein gene in the differentiating mammary gland.

Journal article
Authors Marie Kannius-Janson
Eva M. Johansson
Gunnar Bjursell
Jeanette Nilsson
Published in The Journal of biological chemistry
Volume 277
Issue 20
Pages 17589-96
ISSN 0021-9258
Publication year 2002
Published at Department of Cell and Molecular Biology
Pages 17589-96
Language en
Keywords Alternative Splicing, Animals, Blotting, Western, Breast, growth & development, CCAAT-Enhancer-Binding Proteins, physiology, Carboxylesterase, Carboxylic Ester Hydrolases, genetics, Cell Differentiation, DNA-Binding Proteins, Female, Gene Expression Regulation, Mice, Mice, Inbred C57BL, Mice, Inbred CBA, Milk Proteins, genetics, NFI Transcription Factors, Nuclear Proteins, Rats, Transcription Factors, Transfection, Tumor Cells, Cultured, Y-Box-Binding Protein 1
Subject categories Biological Sciences


Members of the nuclear factor 1 (NF1) transcription factor family have been postulated to be involved in the regulation of milk genes. In this work we have been able to identify the splice variant NF1-C2 as an important member of a tissue-specific activating complex that regulates the milk gene encoding carboxyl ester lipase (CEL). Mutation of the NF1-binding site in the CEL gene promoter results in a drastic reduction of the gene expression to about 15% in mammary epithelial cells. Furthermore, we demonstrate that the NF1-C2 protein interacts with a higher affinity to the NF1-binding site in the CEL gene promoter than other NF1 family members do and that NF1-C2 in the mouse mammary gland is a phosphorylated protein. During development of the mouse mammary gland, binding of NF1-C2 to the CEL gene promoter is induced at midpregnancy, in correlation with the induction of CEL gene expression. The fact that the NF1-C2 involving complex remains throughout the lactation period and decreases during the weaning period, when the CEL gene is down-regulated, supports its importance in the regulation of CEL gene expression. To our knowledge, this is the first report identifying a specific, endogenously expressed NF1 isoform to be involved in the tissue-specific activation of a gene.

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