Expression of the murine RanBP1 and Htf9-c genes is regulated from a shared bidirectional promoter during cell cycle progression

Abstract

The murine Htf9-a/RanBP1and 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-cgene 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-cgenes in a common window of the cell cycle.

BAL1 and BBAP Are Regulated by a Gamma Interferon-Responsive Bidirectional Promoter and Are Overexpressed in Diffuse Large B-Cell Lymphomas with a Prominent Inflammatory Infiltrate

“…For example, bidirectional promoters (i) maintain stoichiometric quantities of transcribed genes (5), (ii) drive the transcription of genes involved in the same cellular pathway or/and activated by the same cellular signal (14), and/or (iii) regulate the expression of genes that need to be sequentially activated (21). In this regard, the bidirectional BAL1/BBAP promoter ensures tightly coordinated transcriptional regulation of the BAL1/ BBAP complex in response to IFN-␥.…”

Diminished dosage of 22q11 genes disrupts neurogenesis and cortical development in a mouse model of 22q11 deletion/DiGeorge syndrome

“…We evaluated candidates by noting their putative cell-cycle function, selective expression in the cortical VZ/SVZ, and maximal expression during neurogenesis. Five 22q11 genes are thought to regulate the cell cycle: Ranbp1 (14), Cdc45l (15), Hira (16), Ufd1l (17), and Sept5 (18); a sixth gene with unknown function, Htf9c, shares a promoter with Ranbp1 (19), and thus, was also analyzed. Ranbp1 and Cdc45l are specifically and robustly expressed in the VZ/SVZ (Fig.…”

An Abundance of Bidirectional Promoters in the Human Genome

“…For example, some bidirectional promoters serve to maintain a stoichiometric relationship, such as the histone genes (Albig et al 1997;Ahn and Gruen 1999;Maxson et al 1983), whereas others regulate the coexpression of genes that function in the same biological pathway (Schmidt et al 1993;Sugimoto et al 1994;Momota et al 1998), or to control expression through different timepoints such as genes involved in the cell cycle (Guarguaglini et al 1997). Other bidirectional promoters provide coordinated responses to induction signals such as heat shock (Hansen et al 2003).…”