Novel genes in cell cycle control and lipid metabolism with dynamically regulated binding sites for sterol regulatory element-binding protein 1 and RNA polymerase II in HepG2 cells detected by chromatin immunoprecipitation with microarray detection.
Sterol regulatory element-binding proteins 1 and 2 (SREBP-1 and SREBP-2) are important regulators of genes involved in cholesterol and fatty acid metabolism, but have also been implicated in the regulation of the cell cycle and have been associated with the pathogenesis of type 2 diabetes, atherosclerosis and obesity, among others. In this study, we aimed to characterize the binding sites of SREBP-1 and RNA polymerase II through chromatin immunoprecipitation and microarray analysis in 1% of the human genome, as defined by the Encyclopaedia of DNA Elements consortium, in a hepatocellular carcinoma cell line (HepG2). Our data identified novel binding sites for SREBP-1 in genes directly or indirectly involved in cholesterol metabolism, e.g. apolipoprotein C-III (APOC3). The most interesting biological findings were the binding sites for SREBP-1 in genes for host cell factor C1 (HCFC1), involved in cell cycle regulation, and for filamin A (FLNA). For RNA polymerase II, we found binding sites at classical promoters, but also in intergenic and intragenic regions. Furthermore, we found evidence of sterol-regulated binding of SREBP-1 and RNA polymerase II to HCFC1 and FLNA. From the results of this work, we infer that SREBP-1 may be involved in processes other than lipid metabolism.
Motallebipour
Mehdi
M
Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
Enroth
Stefan
S
Punga
Tanel
T
Ameur
Adam
A
Koch
Christoph
C
Dunham
Ian
I
Komorowski
Jan
J
Ericsson
Johan
J
Wadelius
Claes
C
D001665:Binding Sites / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002784:Cholesterol / Q000235:genetics / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D003285:Contractile Proteins / Q000235:genetics* / Q000378:metabolism; D064448:Filamins; D018816:Genes, cdc / Q000502:physiology*; D051863:Host Cell Factor C1 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics*; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism*
D003285:Contractile Proteins; D064448:Filamins; C497692:HCFC1 protein, human; D051863:Host Cell Factor C1; D008840:Microfilament Proteins; D051780:Sterol Regulatory Element Binding Protein 1; D002784:Cholesterol; D012319:RNA Polymerase II