|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 277, Issue 37, 34589-34600, September 13, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Pennington Biomedical Research Center,
Baton Rouge, Louisana 70808
Thermogenesis against cold exposure in mammals
occurs in brown adipose tissue (BAT) through mitochondrial uncoupling
protein (UCP1). Expression of the Ucp1 gene is unique in
brown adipocytes and is regulated tightly. The 5'-flanking region of
the mouse Ucp1 gene contains cis-acting
elements including PPRE, TRE, and four half-site cAMP-responsive
elements (CRE) with BAT-specific enhancer elements. In the course of
analyzing how these half-site CREs are involved in Ucp1 expression, we
found that a DNA regulatory element for NF-E2 overlaps CRE2.
Electrophoretic mobility shift assay and competition assays with
the CRE2 element indicates that nuclear proteins from BAT, inguinal
fat, and retroperitoneal fat tissue interact with the CRE2 motif
(CGTCA) in a specific manner. A supershift assay using an antibody
against the CRE-binding protein (CREB) shows specific affinity to the
complex from CRE2 and nuclear extract of BAT. Additionally, Western
blot analysis for phospho-CREB/ATF1 shows an increase in
phosphorylation of CREB/ATF1 in HIB-1B cells after norepinephrine
treatment. Transient transfection assay using luciferase reporter
constructs also indicates that the two half-site CREs are involved in
transcriptional regulation of Ucp1 in response to
norepinephrine and cAMP. We also show that a second DNA regulatory element for NF-E2 is located upstream of the CRE2 region. This element,
which is found in a similar location in the 5'-flanking region of the
human and rodent Ucp1 genes, shows specific binding to rat
and human NF-E2 by electrophoretic mobility shift assay with nuclear
extracts from brown fat. Co-transfections with an Nfe2l2 expression
vector and a luciferase reporter construct of the Ucp1
enhancer region provide additional evidence that Nfe2l2 is involved in
the regulation of Ucp1 by cAMP-mediated signaling.
Regulatory Motifs for CREB-binding Protein and Nfe2l2
Transcription Factors in the Upstream Enhancer of the Mitochondrial
Uncoupling Protein 1 Gene*
*
This work was supported by National Institutes of Health
Grant HD08431.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.
To whom correspondence should be addressed. Tel.: 225-763-2771;
Fax: 225-763-3030; E-mail: kozaklp@pbrc.edu.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  H. Wang, Y. Zhang, E. Yehuda-Shnaidman, A. V. Medvedev, N. Kumar, K. W. Daniel, J. Robidoux, M. P. Czech, D. J. Mangelsdorf, and S. Collins Liver X Receptor {alpha} Is a Transcriptional Repressor of the Uncoupling Protein 1 Gene and the Brown Fat Phenotype Mol. Cell. Biol., April 1, 2008; 28(7): 2187 - 2200. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Q. Xiao, S. M. Williams, B. E. Grayson, M. M. Glavas, M. A. Cowley, M. S. Smith, and K. L. Grove Excess Weight Gain during the Early Postnatal Period Is Associated with Permanent Reprogramming of Brown Adipose Tissue Adaptive Thermogenesis Endocrinology, September 1, 2007; 148(9): 4150 - 4159. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Sher, N. Yivgi-Ohana, and J. Orly Transcriptional Regulation of the Cholesterol Side Chain Cleavage Cytochrome P450 Gene (CYP11A1) Revisited: Binding of GATA, Cyclic Adenosine 3',5'-Monophosphate Response Element-Binding Protein and Activating Protein (AP)-1 Proteins to a Distal Novel Cluster of cis-Regulatory Elements Potentiates AP-2 and Steroidogenic Factor-1-Dependent Gene Expression in the Rodent Placenta and Ovary Mol. Endocrinol., April 1, 2007; 21(4): 948 - 962. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Voss-Andreae, J. G. Murphy, K. L. J. Ellacott, R. C. Stuart, E. A. Nillni, R. D. Cone, and W. Fan Role of the Central Melanocortin Circuitry in Adaptive Thermogenesis of Brown Adipose Tissue Endocrinology, April 1, 2007; 148(4): 1550 - 1560. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-H. Lee, A. Dobrzyn, P. Dobrzyn, S. M. Rahman, M. Miyazaki, and J. M. Ntambi Lack of stearoyl-CoA desaturase 1 upregulates basal thermogenesis but causes hypothermia in a cold environment J. Lipid Res., September 1, 2004; 45(9): 1674 - 1682. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Rim, B. Xue, B. Gawronska-Kozak, and L. P. Kozak Sequestration of Thermogenic Transcription Factors in the Cytoplasm during Development of Brown Adipose Tissue J. Biol. Chem., June 11, 2004; 279(24): 25916 - 25926. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. CANNON and J. NEDERGAARD Brown Adipose Tissue: Function and Physiological Significance Physiol Rev, January 1, 2004; 84(1): 277 - 359. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Kronke, V. N. Bochkov, J. Huber, F. Gruber, S. Bluml, A. Furnkranz, A. Kadl, B. R. Binder, and N. Leitinger Oxidized Phospholipids Induce Expression of Human Heme Oxygenase-1 Involving Activation of cAMP-responsive Element-binding Protein J. Biol. Chem., December 19, 2003; 278(51): 51006 - 51014. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Coulter, C. M. Bearden, X. Liu, R. A. Koza, and L. P. Kozak Dietary fat interacts with QTLs controlling induction of Pgc-1{alpha} and Ucp1 during conversion of white to brown fat Physiol Genomics, July 7, 2003; 14(2): 139 - 147. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |