Repression of virus-induced interferon A promoters by homeodomain transcription factor Ptx1.
Interferon A (IFN-A) genes are differentially expressed after virus induction. The differential expression of individual IFN-A genes is modulated by substitutions in the proximal positive virus responsive element A (VRE-A) of their promoters and by the presence or absence of a distal negative regulatory element (DNRE). The functional feature of the DNRE is to specifically act by repression of VRE-A activity. With the use of the yeast one-hybrid system, we describe here the identification of a specific DNRE-binding protein, the pituitary homeobox 1 (Ptx1 or Pitx1). Ptx1 is detectable in different cell types that differentially express IFN-A genes, and the endogenous Ptx1 protein binds specifically to the DNRE. Upon virus induction, Ptx1 negatively regulates the transcription of DNRE-containing IFN-A promoters, and the C-terminal region, as well as the homeodomain of the Ptx1 protein, is required for this repression. After virus induction, the expression of the Ptx1 antisense RNA leads to a significant increase of endogenous IFN-A gene transcription and is able to modify the pattern of differential expression of individual IFN-A genes. These studies suggest that Ptx1 contributes to the differential transcriptional strength of the promoters of different IFN-A genes and that these genes may provide new targets for transcriptional regulation by a homeodomain transcription factor.
Lopez
S
S
Laboratoire de Régulation de la Transcription et Maladies Génétiques, CNRS, UPR 2228, UFR Biomédicale des Saints-Pères, Université René Descartes, 75270 Paris Cedex 06, France. Sebastien.Navarro@biomedicale.univ-paris5.fr
Island
M L
ML
Drouin
J
J
Bandu
M T
MT
Christeff
N
N
Darracq
N
N
Barbey
R
R
Doly
J
J
Thomas
D
D
Navarro
S
S
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D004247:DNA / Q000235:genetics / Q000378:metabolism; D015342:DNA Probes; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020868:Gene Silencing; D017930:Genes, Reporter; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007370:Interferon Type I / Q000235:genetics*; D051379:Mice; D009522:Newcastle disease virus / Q000502:physiology; D051761:Paired Box Transcription Factors; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016372:RNA, Antisense / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020218:Response Elements / Q000235:genetics; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D020798:Two-Hybrid System Techniques
D015342:DNA Probes; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D007370:Interferon Type I; D051761:Paired Box Transcription Factors; D016372:RNA, Antisense; D012097:Repressor Proteins; D014157:Transcription Factors; C101485:homeobox protein PITX1; D004247:DNA