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 prot ein, a major partner of the Ran GTPase. The divergently transcribed Ht f9-c gene encodes a protein sharing similarity with yeast and bacteria l nucleic acid-modifying enzymes. We report here that both mRNA specie s produced by the Htf9-associated genes are regulated during the cell cycle progression, peak in S phase and decrease during mitosis. Transi ent expression experiments with reporter constructs showed that cell c ycle expression is controlled at the transcriptional level, because th e bidirectional Htf9 promoter is downregulated in growth-arrested cell s, is activated at the G(1)/S transition and reaches maximal activity in S phase, though with a different efficiency for each orientation. W e have delimited specific promoter regions controlling S phase activit y in one or both orientations: identified elements contain recognition sites for members belonging to both the E2F and Spl families of trans cription factors. Together, the results suggest that the sharing of th e regulatory region supports co-regulation of the Htf9-a/RanBP1 and Ht f9-c genes in a common window of the cell cycle.