Transcriptional regulation of mitochondrial glycerophosphate acyltransferase is mediated by distal promoter via ChREBP and SREBP-1.
We have recently identified two promoters, distal and proximal for rat mitochondrial glycerophosphate acyltransferase (mtGPAT). Here we are reporting further characterization of the promoters. Insulin and epidermal growth factor (EGF) stimulated while leptin and glucagon inhibited the luciferase activity of the distal promoter and the amounts of the distal transcript. Conversely, luciferase activity of the proximal promoter and proximal transcript remained unchanged due to these treatments. Only the distal promoter has binding sites for carbohydrate response element binding protein (ChREBP) and sterol regulatory element binding protein-1 (SREBP-1). Electromobility shift assays and chromatin immunoprecipitation assays demonstrated that ChREBP and SREBP-1 bind to the mtGPAT distal promoter. Insulin and EGF increased while glucagon and leptin decreased the binding of SREBP-1 and ChREBP to the distal promoter. Thus, the distal promoter is the regulatory promoter while the proximal promoter acts constitutively for rat mtGPAT gene under the influence of hormones and growth factor.
Guha
Prajna
P
Department of Biological Sciences, St. John's University, Queens, NY 11439, USA.
Aneja
Kawalpreet K
KK
Shilpi
Rasheda Y
RY
Haldar
Dipak
D
D000818:Animals; D001483:Base Sequence; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism*; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005934:Glucagon / Q000494:pharmacology; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000235:genetics*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D020738:Leptin / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics; D008930:Mitochondria, Liver / Q000201:enzymology*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism*; D014158:Transcription, Genetic
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D017931:DNA Primers; D007328:Insulin; D020738:Leptin; C442825:Mlxipl protein, rat; D012333:RNA, Messenger; C497389:Srebf1 protein, rat; D051780:Sterol Regulatory Element Binding Protein 1; D004815:Epidermal Growth Factor; D005934:Glucagon; D008156:Luciferases; D005992:Glycerol-3-Phosphate O-Acyltransferase
Genes Dev. 2000 Apr 15;14(8):963-80
10783168
Biochem Biophys Res Commun. 2005 Nov 18;337(2):602-9
16199006
FASEB J. 2006 Mar;20(3):434-43
16507761
J Biol Chem. 2002 Sep 6;277(36):33490-500
12087097
Med Hypotheses. 2005;64(2):342-9
15607569
J Biol Chem. 1998 Dec 18;273(51):34422-8
9852109
Cell. 1983 Jan;32(1):7-22
6687446
Am J Physiol Endocrinol Metab. 2004 Sep;287(3):E424-30
15100094
J Biol Chem. 1991 May 15;266(14):9140-4
1709163
Prog Lipid Res. 2004 Mar;43(2):134-76
14654091
J Biol Chem. 1994 Apr 8;269(14):10475-84
7908293
J Biol Chem. 1989 May 5;264(13):7176-84
2565337
Proc Natl Acad Sci U S A. 2004 Nov 2;101(44):15597-602
15496471
Arch Biochem Biophys. 2008 Feb 1;470(1):35-43
18021946
Proc Natl Acad Sci U S A. 2004 May 11;101(19):7281-6
15118080
Mol Endocrinol. 2002 Mar;16(3):469-86
11875105
J Lipid Res. 2004 Jul;45(7):1279-88
15102885
Cytokine. 1999 Aug;11(8):585-92
10433805
J Biol Chem. 1994 Jan 7;269(1):347-57
8276818
Mol Cell Biol. 2002 Dec;22(23):8204-14
12417724
Endocrinology. 2005 Nov;146(11):4690-6
16099860
Trans N Y Acad Sci. 1983;41:173-82
6599355
Biochem J. 1986 Mar 1;234(2):279-84
2872882
Ann N Y Acad Sci. 2000;921:473-7
11193879
Metabolism. 2005 Aug;54(8):1041-7
16092054
J Biol Chem. 2005 May 20;280(20):19527-34
15778226
Nat Genet. 2006 Jun;38(6):626-35
16645617
Nucleic Acids Res. 2006 Jan 1;34(Database issue):D82-5
16381980
J Biol Chem. 2004 May 7;279(19):20314-26
14985368
J Clin Invest. 1997 Mar 1;99(5):838-45
9062340
Biochemistry. 1984 Oct 9;23(21):5036-41
6238627
J Biol Chem. 1999 Apr 9;274(15):10430-8
10187833
Endocrinology. 2002 Feb;143(2):551-7
11796510
Oncogene. 2000 Oct 26;19(45):5173-81
11064454
Nat Rev Cancer. 2007 Oct;7(10):763-77
17882277
Mol Cell Biol. 1999 May;19(5):3760-8
10207099
J Exp Biol. 2000 Feb;203(Pt 4):693-704
10648211
Methods Mol Biol. 2008;457:279-92
19066035
J Biol Chem. 1999 Aug 13;274(33):23577-83
10438539
Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):13476-8
11717416
Biol Reprod. 2003 May;68(5):1649-56
12606333
Mol Cell Endocrinol. 2001 Mar 28;174(1-2):151-66
11306182
J Biol Chem. 2000 Feb 11;275(6):3991-8
10660555
J Biol Chem. 1999 Nov 12;274(46):32725-32
10551830
J Lipid Res. 2005 Apr;46(4):697-705
15627654
J Clin Invest. 2008 Mar;118(3):956-64
18292813
Biochem Biophys Res Commun. 2000 Oct 14;277(1):20-6
11027633