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A PPAR response element regulates transcription of the gene for human adipose differentiation-related protein

Targett-Adams, Paul; McElwee, Marion J; Ehrenborg, Ewa; Gustafsson, Mattias LU ; Palmer, Colin N and McLauchlan, John (2005) In Biochimica et Biophysica Acta, Gene Structure and Expression 1728(1-2). p.95-104
Abstract
Lipid droplets are cytoplasmic organelles which serve as storage sites for neutral lipids. Adipose differentiation-related protein (ADRP) is intrinsically associated with the surface of lipid droplets and is believed to play a major role in the maintenance of lipid stores in non-adipocytes. ADRP abundance is intimately linked to the amount of lipid found within cells and agents which increase the levels of intracellular lipid, such as certain agonists of the peroxisome proliferator-activated receptors (PPARs), also are capable of modulating ADRP gene transcription. However, little is known about the molecular mechanisms and promoter control elements, which regulate the transcription of the human gene. Using a reporter system to investigate... (More)
Lipid droplets are cytoplasmic organelles which serve as storage sites for neutral lipids. Adipose differentiation-related protein (ADRP) is intrinsically associated with the surface of lipid droplets and is believed to play a major role in the maintenance of lipid stores in non-adipocytes. ADRP abundance is intimately linked to the amount of lipid found within cells and agents which increase the levels of intracellular lipid, such as certain agonists of the peroxisome proliferator-activated receptors (PPARs), also are capable of modulating ADRP gene transcription. However, little is known about the molecular mechanisms and promoter control elements, which regulate the transcription of the human gene. Using a reporter system to investigate ADRP transcription, we have identified a PPAR response element (PPRE) with the sequence 5'-AGGTGA A AGGGCG-3' within its promoter region. Mutational analysis revealed that the ADRP PPRE specifically mediated the upregulation of transcription in response to activation by agonists of PPAR subtypes alpha and delta in both rat and human hepatocyte-derived cell lines. These findings offer insight into the mechanisms which serve to regulate ADRP transcription and intracellular lipid storage. (Less)
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author
publishing date
type
Contribution to journal
publication status
published
subject
keywords
PPRE, Promoter, ADRP, Regulation, PPAR
in
Biochimica et Biophysica Acta, Gene Structure and Expression
volume
1728
issue
1-2
pages
95 - 104
publisher
Elsevier
external identifiers
  • pmid:15777674
  • scopus:15744363183
ISSN
0167-4781
DOI
10.1016/j.bbaexp.2005.01.017
language
English
LU publication?
no
id
78c6134c-d201-4d4e-bd73-10fdac62e86f (old id 1133036)
date added to LUP
2008-06-25 14:09:50
date last changed
2017-10-01 04:49:00
@article{78c6134c-d201-4d4e-bd73-10fdac62e86f,
  abstract     = {Lipid droplets are cytoplasmic organelles which serve as storage sites for neutral lipids. Adipose differentiation-related protein (ADRP) is intrinsically associated with the surface of lipid droplets and is believed to play a major role in the maintenance of lipid stores in non-adipocytes. ADRP abundance is intimately linked to the amount of lipid found within cells and agents which increase the levels of intracellular lipid, such as certain agonists of the peroxisome proliferator-activated receptors (PPARs), also are capable of modulating ADRP gene transcription. However, little is known about the molecular mechanisms and promoter control elements, which regulate the transcription of the human gene. Using a reporter system to investigate ADRP transcription, we have identified a PPAR response element (PPRE) with the sequence 5'-AGGTGA A AGGGCG-3' within its promoter region. Mutational analysis revealed that the ADRP PPRE specifically mediated the upregulation of transcription in response to activation by agonists of PPAR subtypes alpha and delta in both rat and human hepatocyte-derived cell lines. These findings offer insight into the mechanisms which serve to regulate ADRP transcription and intracellular lipid storage.},
  author       = {Targett-Adams, Paul and McElwee, Marion J and Ehrenborg, Ewa and Gustafsson, Mattias and Palmer, Colin N and McLauchlan, John},
  issn         = {0167-4781},
  keyword      = {PPRE,Promoter,ADRP,Regulation,PPAR},
  language     = {eng},
  number       = {1-2},
  pages        = {95--104},
  publisher    = {Elsevier},
  series       = {Biochimica et Biophysica Acta, Gene Structure and Expression},
  title        = {A PPAR response element regulates transcription of the gene for human adipose differentiation-related protein},
  url          = {http://dx.doi.org/10.1016/j.bbaexp.2005.01.017},
  volume       = {1728},
  year         = {2005},
}