Expression of the murine RanBP1 and Htf9-c genes is regulated from a shared bidirectional promoter during cell cycle progression.
The murine Htf9-a/RanBP1 and Htf9-c genes are divergently transcribed from a bidirectional promoter. The Htf9-a gene encodes the RanBP1 protein, a major partner of the Ran GTPase. The divergently transcribed Htf9-c gene encodes a protein sharing similarity with yeast and bacterial nucleic acid-modifying enzymes. We report here that both mRNA species produced by the Htf9-associated genes are regulated during the cell cycle progression, peak in S phase and decrease during mitosis. Transient expression experiments with reporter constructs showed that cell cycle expression is controlled at the transcriptional level, because the bidirectional Htf9 promoter is down-regulated in growth-arrested cells, is activated at the G1/S transition and reaches maximal activity in S phase, though with a different efficiency for each orientation. We have delimited specific promoter regions controlling S phase activity in one or both orientations: identified elements contain recognition sites for members belonging to both the E2F and Sp1 families of transcription factors. Together, the results suggest that the sharing of the regulatory region supports co-regulation of the Htf9-a/RanBP1 and Htf9-c genes in a common window of the cell cycle.
Guarguaglini
G
G
CNR Centre of Evolutionary Genetics, c/o Department of Genetics and Molecular Biology, University 'La Sapienza', Via degli Apuli 4, Rome 00185, Italy.
Battistoni
A
A
Pittoggi
C
C
Di Matteo
G
G
Di Fiore
B
B
Lavia
P
P
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D047390:Casein Kinase II; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*; D005786:Gene Expression Regulation; D006918:Hydroxyurea / Q000494:pharmacology; D016350:Leucine Zippers; D051379:Mice; D008969:Molecular Sequence Data; D015739:Nocodazole / Q000494:pharmacology; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D011493:Protein Kinase C / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011506:Proteins / Q000737:chemistry / Q000235:genetics*; D016601:RNA-Binding Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic / Q000187:drug effects; D020931:ran GTP-Binding Protein
D009687:Nuclear Proteins; D011506:Proteins; D016601:RNA-Binding Proteins; C091775:ran-binding protein 1; C070847:Htf9c protein, mouse; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D020931:ran GTP-Binding Protein; D015739:Nocodazole; D006918:Hydroxyurea