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CCAAT/enhancer-binding protein alpha is required for transcription of the beta 3-adrenergic receptor gene during adipogenesis.

Publication ,  Journal Article
Dixon, TM; Daniel, KW; Farmer, SR; Collins, S
Published in: J Biol Chem
January 5, 2001

The beta(3)-adrenergic receptor (beta(3)AR) is expressed predominantly in adipocytes, and it plays a major role in regulating lipolysis and adaptive thermogenesis. Its expression in a variety of adipocyte cell models is preceded by the appearance of CCAAT/enhancer-binding protein alpha (C/EBP alpha), which has been shown to regulate a number of other adipocyte-specific genes. Importantly, it has been demonstrated that several adipocyte cell lines that fail to express C/EBP alpha exhibit reduced insulin sensitivity, despite an apparent adipogenic phenotype. Here we show that transcription and function of the beta(3)AR correlates with C/EBP alpha expression in these adipocyte models. A 5.13-kilobase pair fragment of the mouse beta(3)AR promoter was isolated and sequenced. This fragment conferred a 50-fold increase in luciferase reporter gene expression in adipocytes. Two putative C/EBP binding sites exist at -3306 to -3298 and at -1462 to -1454, but only the more distal site is functional. Oligonucleotides corresponding to both the wild-type and mutated -3306 element were inserted upstream of a thymidine kinase luciferase construct. When cotransfected in fibroblasts with a C/EBP alpha expression vector, reporter gene expression increased 3-fold only in the wild-type constructs. The same mutation, when placed into the intact 5.13-kilobase pair promoter, reduced promoter activity in adipocytes from 50-fold to <10-fold. Electrophoretic mobility shift analysis demonstrated that the site at -3306 generated a specific protein-oligonucleotide complex that was supershifted by C/EBP alpha antibody, while a probe corresponding to a putative site at -1462 did not. These results define C/EBP alpha as a key transcriptional regulator of the mouse beta(3)AR gene during adipogenesis.

Duke Scholars

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

January 5, 2001

Volume

276

Issue

1

Start / End Page

722 / 728

Location

United States

Related Subject Headings

  • Transfection
  • Sequence Analysis, DNA
  • Response Elements
  • Receptors, Adrenergic, beta-3
  • RNA, Messenger
  • Promoter Regions, Genetic
  • Organ Specificity
  • Mutation
  • Molecular Sequence Data
  • Mice
 

Citation

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Dixon, T. M., Daniel, K. W., Farmer, S. R., & Collins, S. (2001). CCAAT/enhancer-binding protein alpha is required for transcription of the beta 3-adrenergic receptor gene during adipogenesis. J Biol Chem, 276(1), 722–728. https://doi.org/10.1074/jbc.M008440200
Dixon, T. M., K. W. Daniel, S. R. Farmer, and S. Collins. “CCAAT/enhancer-binding protein alpha is required for transcription of the beta 3-adrenergic receptor gene during adipogenesis.J Biol Chem 276, no. 1 (January 5, 2001): 722–28. https://doi.org/10.1074/jbc.M008440200.
Dixon, T. M., et al. “CCAAT/enhancer-binding protein alpha is required for transcription of the beta 3-adrenergic receptor gene during adipogenesis.J Biol Chem, vol. 276, no. 1, Jan. 2001, pp. 722–28. Pubmed, doi:10.1074/jbc.M008440200.
Dixon TM, Daniel KW, Farmer SR, Collins S. CCAAT/enhancer-binding protein alpha is required for transcription of the beta 3-adrenergic receptor gene during adipogenesis. J Biol Chem. 2001 Jan 5;276(1):722–728.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

January 5, 2001

Volume

276

Issue

1

Start / End Page

722 / 728

Location

United States

Related Subject Headings

  • Transfection
  • Sequence Analysis, DNA
  • Response Elements
  • Receptors, Adrenergic, beta-3
  • RNA, Messenger
  • Promoter Regions, Genetic
  • Organ Specificity
  • Mutation
  • Molecular Sequence Data
  • Mice