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J. Biol. Chem., Vol. 277, Issue 20, 17589-17596, May 17, 2002
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From the Department of CMB/Molecular Biology, Box 462, S-405 30 Göteborg, Sweden
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.
Nuclear Factor 1-C2 Contributes to the Tissue-specific Activation
of a Milk Protein Gene in the Differentiating Mammary Gland*
§,,
*
This work was supported by grants from the Swedish Medical
Research Council, Assar Gabrielsson Foundation, and Fredrik and Ingrid
Thuring Foundation.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Both authors contributed equally to this work.
§
To whom correspondence should be addressed. Tel.: 46 31 7733805;
Fax: 46 31 7733801; E-mail: Marie.Kannius@molbio.gu.se.
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