ERH (enhancer of rudimentary homologue), a conserved factor identical between frog and human, is a transcriptional repressor

Drosophila enhancer of rudimentary [e(r)] interacts genetically with the ru dimentary gene, which encodes a protein possessing the first three enzymati c activities of the pyrimidine biosynthesis pathway. A regulatory or enzyma tic activity of e(r) in pyrimidine biosynthesis and the cell cycle has been suggested, but nothing is known about its molecular function. The factor i s evolutionarily highly conserved since homologues exist in plants and mamm als. We cloned the (X) under bar enopus (e) under bar nhancer of (r) under bar udimentary homologue (XERH) as an interaction partner of DCoH/PCD ((d) under bar imerisation (c) under bar ofactor of (H) under bar NFl/(p) under bar terin-4 alpha-(c) under bar arbino-lamine (d) under bar ehydratase) in the yeast two-hybrid assay. DCoH/PCD is a multifunctional factor originally identified as a positive cofactor of the HNF1 homeobox transcription facto rs. XERH is a 104 amino acid protein that is identical to its mammalian hom ologues. The mRNA is expressed maternally, enriched in ectodermal derivativ es during development and ubiquitously detectable in the adult. Fused to th e DNA binding region of the GAL4 transcription factor domain, XERH represse s the activity of a GAL4 responsive reporter in HeLa, but not in N1H3T3 cel ls. Furthermore, the DCoH/PCD coactivation of a HNF1 responsive reporter is inhibited by XERH. We propose that XERH is a cell type-specific transcript ional repressor, probably interfering with HNF1-dependent gene regulation v ia DCoH/PCD.