After transiting to the nucleus SREBPs (SREBP1A/1C/2, SREBFs) bind short sequences, sterol regulatory elements (SREs), in the promoters of target genes (reviewed in Eberle et al. 2004, Weber et al. 2004). SREBPs alone are relatively weak activators of transcription, with SREBP1C being significantly weaker than SREBP1A or SREBP2. In combination with other transcription factors such as SP1 and NF-Y the SREBPs are much stronger activators. SREBP1C seems to more specifically target genes involved in fatty acid synthesis while SREBP2 seems to target genes involved in cholesterol synthesis (Pai et al. 1998).
View original pathway at Reactome.
Jiang G, McKenzie TL, Conrad DG, Shechter I.; ''Transcriptional regulation by lovastatin and 25-hydroxycholesterol in HepG2 cells and molecular cloning and expression of the cDNA for the human hepatic squalene synthase.''; PubMedEurope PMCScholia
Magaña MM, Lin SS, Dooley KA, Osborne TF.; ''Sterol regulation of acetyl coenzyme A carboxylase promoter requires two interdependent binding sites for sterol regulatory element binding proteins.''; PubMedEurope PMCScholia
Horton JD, Goldstein JL, Brown MS.; ''SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver.''; PubMedEurope PMCScholia
Reed BD, Charos AE, Szekely AM, Weissman SM, Snyder M.; ''Genome-wide occupancy of SREBP1 and its partners NFY and SP1 reveals novel functional roles and combinatorial regulation of distinct classes of genes.''; PubMedEurope PMCScholia
Juge-Aubry C, Pernin A, Favez T, Burger AG, Wahli W, Meier CA, Desvergne B.; ''DNA binding properties of peroxisome proliferator-activated receptor subtypes on various natural peroxisome proliferator response elements. Importance of the 5'-flanking region.''; PubMedEurope PMCScholia
Li J, Ding SF, Habib NA, Fermor BF, Wood CB, Gilmour RS.; ''Partial characterization of a cDNA for human stearoyl-CoA desaturase and changes in its mRNA expression in some normal and malignant tissues.''; PubMedEurope PMCScholia
Abu-Elheiga L, Jayakumar A, Baldini A, Chirala SS, Wakil SJ.; ''Human acetyl-CoA carboxylase: characterization, molecular cloning, and evidence for two isoforms.''; PubMedEurope PMCScholia
Bennett MK, Lopez JM, Sanchez HB, Osborne TF.; ''Sterol regulation of fatty acid synthase promoter. Coordinate feedback regulation of two major lipid pathways.''; PubMedEurope PMCScholia
Shimano H, Yahagi N, Amemiya-Kudo M, Hasty AH, Osuga J, Tamura Y, Shionoiri F, Iizuka Y, Ohashi K, Harada K, Gotoda T, Ishibashi S, Yamada N.; ''Sterol regulatory element-binding protein-1 as a key transcription factor for nutritional induction of lipogenic enzyme genes.''; PubMedEurope PMCScholia
Chambliss KL, Slaughter CA, Schreiner R, Hoffmann GF, Gibson KM.; ''Molecular cloning of human phosphomevalonate kinase and identification of a consensus peroxisomal targeting sequence.''; PubMedEurope PMCScholia
Toth MJ, Huwyler L.; ''Molecular cloning and expression of the cDNAs encoding human and yeast mevalonate pyrophosphate decarboxylase.''; PubMedEurope PMCScholia
Jayakumar A, Tai MH, Huang WY, al-Feel W, Hsu M, Abu-Elheiga L, Chirala SS, Wakil SJ.; ''Human fatty acid synthase: properties and molecular cloning.''; PubMedEurope PMCScholia
Wilkin DJ, Kutsunai SY, Edwards PA.; ''Isolation and sequence of the human farnesyl pyrophosphate synthetase cDNA. Coordinate regulation of the mRNAs for farnesyl pyrophosphate synthetase, 3-hydroxy-3-methylglutaryl coenzyme A reductase, and 3-hydroxy-3-methylglutaryl coenzyme A synthase by phorbol ester.''; PubMedEurope PMCScholia
Abu-Elheiga L, Almarza-Ortega DB, Baldini A, Wakil SJ.; ''Human acetyl-CoA carboxylase 2. Molecular cloning, characterization, chromosomal mapping, and evidence for two isoforms.''; PubMedEurope PMCScholia
Villagra A, Ulloa N, Zhang X, Yuan Z, Sotomayor E, Seto E.; ''Histone deacetylase 3 down-regulates cholesterol synthesis through repression of lanosterol synthase gene expression.''; PubMedEurope PMCScholia
Choi WI, Jeon BN, Park H, Yoo JY, Kim YS, Koh DI, Kim MH, Kim YR, Lee CE, Kim KS, Osborne TF, Hur MW.; ''Proto-oncogene FBI-1 (Pokemon) and SREBP-1 synergistically activate transcription of fatty-acid synthase gene (FASN).''; PubMedEurope PMCScholia
Xuan JW, Kowalski J, Chambers AF, Denhardt DT.; ''A human promyelocyte mRNA transiently induced by TPA is homologous to yeast IPP isomerase.''; PubMedEurope PMCScholia
Pai JT, Guryev O, Brown MS, Goldstein JL.; ''Differential stimulation of cholesterol and unsaturated fatty acid biosynthesis in cells expressing individual nuclear sterol regulatory element-binding proteins.''; PubMedEurope PMCScholia
Amemiya-Kudo M, Shimano H, Hasty AH, Yahagi N, Yoshikawa T, Matsuzaka T, Okazaki H, Tamura Y, Iizuka Y, Ohashi K, Osuga J, Harada K, Gotoda T, Sato R, Kimura S, Ishibashi S, Yamada N.; ''Transcriptional activities of nuclear SREBP-1a, -1c, and -2 to different target promoters of lipogenic and cholesterogenic genes.''; PubMedEurope PMCScholia
Tabor DE, Kim JB, Spiegelman BM, Edwards PA.; ''Identification of conserved cis-elements and transcription factors required for sterol-regulated transcription of stearoyl-CoA desaturase 1 and 2.''; PubMedEurope PMCScholia
Ohno Y, Suto S, Yamanaka M, Mizutani Y, Mitsutake S, Igarashi Y, Sassa T, Kihara A.; ''ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingolipid synthesis.''; PubMedEurope PMCScholia
Shin ES, Lee HH, Cho SY, Park HW, Lee SJ, Lee TR.; ''Genistein downregulates SREBP-1 regulated gene expression by inhibiting site-1 protease expression in HepG2 cells.''; PubMedEurope PMCScholia
Rome S, Lecomte V, Meugnier E, Rieusset J, Debard C, Euthine V, Vidal H, Lefai E.; ''Microarray analyses of SREBP-1a and SREBP-1c target genes identify new regulatory pathways in muscle.''; PubMedEurope PMCScholia
Inoue J, Sato R, Maeda M.; ''Multiple DNA elements for sterol regulatory element-binding protein and NF-Y are responsible for sterol-regulated transcription of the genes for human 3-hydroxy-3-methylglutaryl coenzyme A synthase and squalene synthase.''; PubMedEurope PMCScholia
Ericsson J, Jackson SM, Edwards PA.; ''Synergistic binding of sterol regulatory element-binding protein and NF-Y to the farnesyl diphosphate synthase promoter is critical for sterol-regulated expression of the gene.''; PubMedEurope PMCScholia
Vock C, Döring F, Nitz I.; ''Transcriptional regulation of HMG-CoA synthase and HMG-CoA reductase genes by human ACBP.''; PubMedEurope PMCScholia
Vallett SM, Sanchez HB, Rosenfeld JM, Osborne TF.; ''A direct role for sterol regulatory element binding protein in activation of 3-hydroxy-3-methylglutaryl coenzyme A reductase gene.''; PubMedEurope PMCScholia
Lu B, Jiang YJ, Kim P, Moser A, Elias PM, Grunfeld C, Feingold KR.; ''Expression and regulation of GPAT isoforms in cultured human keratinocytes and rodent epidermis.''; PubMedEurope PMCScholia
Wassif CA, Maslen C, Kachilele-Linjewile S, Lin D, Linck LM, Connor WE, Steiner RD, Porter FD.; ''Mutations in the human sterol delta7-reductase gene at 11q12-13 cause Smith-Lemli-Opitz syndrome.''; PubMedEurope PMCScholia
Nagai M, Sakakibara J, Nakamura Y, Gejyo F, Ono T.; ''SREBP-2 and NF-Y are involved in the transcriptional regulation of squalene epoxidase.''; PubMedEurope PMCScholia
Matsushima M, Inazawa J, Takahashi E, Suzumori K, Nakamura Y.; ''Molecular cloning and mapping of a human cDNA (SC5DL) encoding a protein homologous to fungal sterol-C5-desaturase.''; PubMedEurope PMCScholia
Schafer BL, Bishop RW, Kratunis VJ, Kalinowski SS, Mosley ST, Gibson KM, Tanaka RD.; ''Molecular cloning of human mevalonate kinase and identification of a missense mutation in the genetic disease mevalonic aciduria.''; PubMedEurope PMCScholia
Ishimoto K, Tachibana K, Hanano I, Yamasaki D, Nakamura H, Kawai M, Urano Y, Tanaka T, Hamakubo T, Sakai J, Kodama T, Doi T.; ''Sterol-regulatory-element-binding protein 2 and nuclear factor Y control human farnesyl diphosphate synthase expression and affect cell proliferation in hepatoblastoma cells.''; PubMedEurope PMCScholia
Schiavoni G, Bennati AM, Castelli M, Della Fazia MA, Beccari T, Servillo G, Roberti R.; ''Activation of TM7SF2 promoter by SREBP-2 depends on a new sterol regulatory element, a GC-box, and an inverted CCAAT-box.''; PubMedEurope PMCScholia
Oh SY, Park SK, Kim JW, Ahn YH, Park SW, Kim KS.; ''Acetyl-CoA carboxylase beta gene is regulated by sterol regulatory element-binding protein-1 in liver.''; PubMedEurope PMCScholia
Nakamura Y, Sakakibara J, Izumi T, Shibata A, Ono T.; ''Transcriptional regulation of squalene epoxidase by sterols and inhibitors in HeLa cells.''; PubMedEurope PMCScholia
Harada N, Fujimoto E, Okuyama M, Sakaue H, Nakaya Y.; ''Identification and functional characterization of human glycerol-3-phosphate acyltransferase 1 gene promoters.''; PubMedEurope PMCScholia
Wang M, Yang F, Zhang X, Zhao H, Wang Q, Pan Y.; ''Comparative analysis of MTF-1 binding sites between human and mouse.''; PubMedEurope PMCScholia
Zhao Y, Yu L, Gao J, Fu Q, Hua Y, Zhang H, Zhao S.; ''cDNA cloning, chromosome mapping and expression characterization of human geranylgeranyl pyrophosphate synthase.''; PubMedEurope PMCScholia
Strömstedt M, Rozman D, Waterman MR.; ''The ubiquitously expressed human CYP51 encodes lanosterol 14 alpha-demethylase, a cytochrome P450 whose expression is regulated by oxysterols.''; PubMedEurope PMCScholia
MED1 is a component of each of the various Mediator complexes, that function as transcription co-activators. The MED1-containing compolexes include the DRIP, ARC, TRIP and CRSP compllexes.
Peroxisome proliferator receptor elements bind heterodimers containing a peroxisome proliferator receptor and a retinoic acid receptor. The consensus sequence is TGAMCTTTGNCCTAGWTYYG.
The SCD gene is transcribed to yield mRNA (Li et al. 1994) and the mRNA is translated to yield protein. The SREBP1A (SREBF1A) and SREBP1C (SREBF1C) transcription factors bind the promoter of the SCD gene and activate transcription in response to low cellular cholesterol (Tabor et al. 1999, Bee et al. 2001).
SREBP2 (SREBF2) binds and transactivates an unusual sterol regulatory element in the promoter of the TM7SF2 gene (Schiavoni et al. 2010). NF-Y binds the promoter and is important for activation by SREBP2. SREBP1A and SREBP1C can also bind the TM7SF2 promoter (Reed et al. 2008, Rome et al. 2008).
SREBP1A/1C/2 (SREBF1A/1C/2), together with NF-Y and SP1, bind and transactivate the promoter of the FDFT1 gene (Inoue et al. 1998, Pai et al. 1998, Reed et al. 2008, Rome et al. 2008). SREBP2 activates FDFT1 more strongly than does SREBP1A (Pai et al. 1998).
SREBP1A/1C/2 (SREBF1A/1C/2), together with NF-Y, bind and transactivate the promoter of the FDPS gene (Ericsson et al. 1996, Pai et al. 1998, Amemiya-Kudo et al. 2002, Reed et al. 2008, Rome et al. 2008, Ishimoto et al. 2010). The binding of NF-Y synergistically enhances the binding of SREBP1 (Ericsson et al. 1996). SREBP1A activates FDPS more strongly than does SREBP2 or SREBP1C (Amemiya-Kudo et al. 2002).
SREBP1A (SREBF1A) or SREBP1C, together with NF-Y and SP1, bind and transactivate the promoter of the FASN gene (Bennett et al. 1995, Pai et al. 1998, Xiong et al. 2000, Amemiya-Kudo et al. 2002, Shin et al. 2007, Choi et al. 2008, Rome et al. 2008). NF-Y is required for response to cholesterol (Xiong et al. 2000). SREBP1A activates FASN more strongly than does SREBP1C or SREBP2 (Pai et al. 1998, Amemiya-Kudo et al. 2002).
SREBP1A/1C/2 (SREBF1A/1C/2), together with NF-Y, bind and transactivate the promoter of the HMGCS1 gene (Maeda et al. 1998, Pai et al. 1998, Amemiya-Kudo et al. 2002, Reed et al. 2008). SREBP1A and SREBP2 activate HMGCS1 equally (Pai et al. 1998).
SREBP1A (SREBF1A) or SREBP2 binds and transactivates the promoter of the SQLE gene (Reed et al. 2008). The promoter also contains a consensus binding site for NF-Y (Nagai et al. 2002).
SREBP1A (SREBF1A) or SREBP2 binds and transactivates the promoter of the LSS gene (Pai et al. 1998, Rome et al. 2008). SREBP1A and SREBP2 activate LSS equally (Pai et al. 1998).
SREBP1A (SREBF1A) or SREBP1C bind and transactivate promoter II of the GPAM gene (Harada et al. 2012). Promoter II is active in lipogenic tissues. As inferred from mouse, NF-Y also binds the GPAM promoter with SREBP1A/1C.
SREBP1A (SREBF1A) or SREBP1C bind two sites in the promoter of the ACACA gene (Magana et al. 1997, Rome et al. 2008). Each site is required for activation of transcription.
SREBP1A (SREBF1A) or SREBP2, together with NF-Y, bind and transactivate the promoter of the HMGCR gene (Vallett et al. 1996, Pai et al. 1998, Reed et al. 2008, Rome et al. 2008). SREBP2 activates HMGCR slightly more than does SREBP1A (Pai et al. 1998). SREBP1A/2 binds 2 main sites and 2 auxiliary sites in the HMGCR promoter (Vallett et al. 1996).
SREBP1A (SREBF1A) or SREBP2, together with NF-Y and SP1, bind and transactivate the promoter of the CYP51A1 gene (Pai et al. 1998, Reed et al. 2008, Rome et al. 2008). SREBP1A and SREBP2 activate CYP51A1 equally (Pai et al. 1998).
SREBF1A (SREBP1A) and SREBF1C (SREBP1C) bind the promoter of the Stearoyl CoA Desaturase 1 (SCD1) gene and enhance transcription (Pai et al. 1998, Shimao et al. 1999, Tabor et al. 1999, Bene et al. 2001, reviewed in Horton et al. 2002).
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dimer:12Zn2+:HMGCR
geneAnnotated Interactions
dimer:12Zn2+:HMGCR
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