Cooperation between NRF-2 and YY-1 transcription factors is essential for triggering the expression of the PREPL-C2ORF34 bidirectional gene pair.
BACKGROUND
Many mammalian genes are organized as bidirectional (head-to-head) gene pairs with the two genes separated only by less than 1 kb. The transcriptional regulation of these bidirectional gene pairs remains largely unclear, but a few studies have suggested that the two closely adjacent genes in divergent orientation can be co-regulated by a single transcription factor binding to a specific regulatory fragment. Here we report an evolutionarily conserved bidirectional gene pair, known as the PREPL-C2ORF34 gene pair, whose transcription relies on the synergic cooperation of two transcription factors binding to an intergenic bidirectional minimal promoter.


RESULTS
While PREPL is present primarily in brain and heart, C2ORF34 is ubiquitously and abundantly expressed in almost all tissues. Genomic analyses revealed that these two non-homologous genes are adjacent in a head-to-head configuration on human chromosome 2p21 and separated by only 405 bp. Within this short intergenic region, a 243-bp GC-rich segment was demonstrated to function as a bidirectional minimal promoter to initiate the transcription of both flanking genes. Two key transcription factors, NRF-2 and YY-1, were further identified to coordinately participate in driving both gene expressions in an additive manner. The functional cooperation between these two transcription factors, along with their genomic binding sites and some cis-acting repressive elements, are essential for the transcriptional activation and tissue distribution of the PREPL-C2ORF34 bidirectional gene pair.


CONCLUSIONS
This study provides new insights into the complex transcriptional mechanism of a mammalian head-to-head gene pair which requires cooperative binding of multiple transcription factors to a bidirectional minimal promoter of the shared intergenic region.
Huang
Chien-Chang
CC
1Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan. james@nhri.org.tw
Chang
Wun-Shaing Wayne
WS
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D015870:Gene Expression; D006801:Humans; D008780:Methyltransferases / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D009928:Organ Specificity; D000085822:Prolyl Oligopeptidases; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D016415:Sequence Alignment; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D052416:Targeted Gene Repair; D050986:YY1 Transcription Factor / Q000235:genetics / Q000378:metabolism*
D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D050986:YY1 Transcription Factor; C494698:YY1 protein, human; D008780:Methyltransferases; C038999:calmodulin-lysine methyltransferase; D012697:Serine Endopeptidases; C000705287:PREPL protein, human; D000085822:Prolyl Oligopeptidases