Members of the nuclear factor 1 family reduce the transcriptional potential of the nuclear receptor LXRalpha promoter.
Expression of the LXRalpha nuclear receptor in liver is predicted to affect cholesterol and lipid metabolism. Here we show that a short fragment from the LXRalpha gene promoter spanning the region from -144 to +43 relative to the mRNA initiation site can drive transcription of a reporter gene. Under basal conditions, in vitro DNase I footprinting demonstrated interaction between nuclear proteins and an NF1 recognition site in close vicinity to the transcriptional initiation. Both supershift, mutational analyses in EMSA and transfections provided evidence that the NF1 (nuclear factor I) transcription factor interacts with the LXRalpha promoter. All four members of the NF1 family were found to suppress the transcriptional activity indicating a general inhibitory effect on LXRalpha expression. A similar regulation by NF1 was also observed when using a fragment from the LXRalpha promoter extending up to position -3033 therefore giving the inhibitory effect of NF1 a significant impact on LXRalpha gene expression.
Steffensen
K R
KR
Department of Biosciences, Novum Research Park, Karolinska Institute, Huddinge, Sweden. knut.steffensen@biosci.ki.se
Holter
E
E
Tobin
K A
KA
Leclerc
S
S
Gustafsson
J A
JA
Guérin
S L
SL
Eskild
W
W
D000818:Animals; D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism*; D002460:Cell Line; D004247:DNA / Q000235:genetics; D018983:DNA Footprinting; D004268:DNA-Binding Proteins; D017930:Genes, Reporter; D008099:Liver / Q000378:metabolism; D000071518:Liver X Receptors; D008156:Luciferases / Q000235:genetics; D051379:Mice; D016296:Mutagenesis; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D057093:Orphan Nuclear Receptors; D011401:Promoter Regions, Genetic; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D051840:Y-Box-Binding Protein 1
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D000071518:Liver X Receptors; D051839:NFI Transcription Factors; C000605213:NR1H3 protein, human; C000605214:Nr1h3 protein, mouse; D009687:Nuclear Proteins; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; D004247:DNA; D008156:Luciferases