Tissue-specific and beta-adrenergic regulation of the mitochondrial uncoupling protein gene: control by cis-acting elements in the 5'- flanking region

1993 ◽  
Vol 7 (4) ◽  
pp. 497-506 ◽  
Author(s):  
A. M. Cassard-Doulcier
Keyword(s):  
Protein Gene ◽  
Uncoupling Protein ◽  
Gene Control ◽  
Mitochondrial Uncoupling ◽  
Tissue Specific ◽  
Adrenergic Regulation ◽  
Cis Acting ◽  
Mitochondrial Uncoupling Protein ◽  
Flanking Region ◽  
Uncoupling Protein Gene

scholarly journals The mitochondrial uncoupling protein gene in brown fat: correlation between DNase I hypersensitivity and expression in transgenic mice.

1991 ◽  
Vol 11 (8) ◽  
pp. 4147-4156 ◽  
Author(s):  
B B Boyer ◽  
L P Kozak
Keyword(s):  
Transgenic Mice ◽  
Protein Gene ◽  
Uncoupling Protein ◽  
Dnase I ◽  
Brown Fat ◽  
Hypersensitive Site ◽  
Mitochondrial Uncoupling ◽  
Mitochondrial Uncoupling Protein ◽  
Dnase I Hypersensitive Site ◽  
Uncoupling Protein Gene

The mitochondrial uncoupling protein gene is rapidly induced in mouse brown fat following cold exposure. To identify cis-regulatory elements, approximately 50 kb of chromatin surrounding the uncoupling protein gene was examined for its hypersensitivity to DNase I. Seven DNase I-hypersensitive sites were identified in the 5'-flanking DNA, and one site was identified in the 3'-flanking DNA. Transgenic mice with an uncoupling protein minigene were generated by microinjection of fertilized eggs with a transgene containing 3 kb of 5'-flanking DNA and 0.3 kb of 3'-flanking DNA. Expression of the transgene is restricted to brown fat and is cold inducible. Four additional transgenic lines were generated with a second transgene containing a 1.8-kb deletion in the 5'-flanking DNA, and expression of this minigene is absent in all tissues analyzed. A DNase I-hypersensitive site located in the 1.8-kb deletion contains a cyclic AMP response element that binds a brown fat tumor enriched nuclear factor. On the basis of these observations, we propose that a cis-acting regulatory sequence between -3 and -1.2 kb of the 5'-flanking region, possibly at a DNase I-hypersensitive site, is required for controlling uncoupling protein expression in vivo.

The mitochondrial uncoupling protein gene in brown fat: correlation between DNase I hypersensitivity and expression in transgenic mice

1991 ◽  
Vol 11 (8) ◽  
pp. 4147-4156
Author(s):  
B B Boyer ◽  
L P Kozak
Keyword(s):  
Transgenic Mice ◽  
Protein Gene ◽  
Uncoupling Protein ◽  
Dnase I ◽  
Brown Fat ◽  
Hypersensitive Site ◽  
Mitochondrial Uncoupling ◽  
Mitochondrial Uncoupling Protein ◽  
Dnase I Hypersensitive Site ◽  
Uncoupling Protein Gene

The mitochondrial uncoupling protein gene is rapidly induced in mouse brown fat following cold exposure. To identify cis-regulatory elements, approximately 50 kb of chromatin surrounding the uncoupling protein gene was examined for its hypersensitivity to DNase I. Seven DNase I-hypersensitive sites were identified in the 5'-flanking DNA, and one site was identified in the 3'-flanking DNA. Transgenic mice with an uncoupling protein minigene were generated by microinjection of fertilized eggs with a transgene containing 3 kb of 5'-flanking DNA and 0.3 kb of 3'-flanking DNA. Expression of the transgene is restricted to brown fat and is cold inducible. Four additional transgenic lines were generated with a second transgene containing a 1.8-kb deletion in the 5'-flanking DNA, and expression of this minigene is absent in all tissues analyzed. A DNase I-hypersensitive site located in the 1.8-kb deletion contains a cyclic AMP response element that binds a brown fat tumor enriched nuclear factor. On the basis of these observations, we propose that a cis-acting regulatory sequence between -3 and -1.2 kb of the 5'-flanking region, possibly at a DNase I-hypersensitive site, is required for controlling uncoupling protein expression in vivo.

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