Elsevier Bidirectional Gene Promoters: Transcription system and chromosomal structure

Recent studies in human genetics and in silico analyses have revealed that a number of genes are head-head orientated with other genes or non-coding RNAs. The expression of regulatory element-containing 5’-upstream regions of gene pairs are referred to as bi-directional promoters and are thought to have a key role in biological regulatory mechanisms. For example, tumor suppressor protein-encoding TP53 and BRCA1 genes are head-head bound with WRAP53 and NBR2, respectively. DNA-repair factor-encoding ATM and PRKDC (DNA-PKcs) genes have bidirectional partner NPAT and MCM4, respectively. Surveillance of the human DNA database has revealed that the numbers of DNA repair/mitochondrial function/immune response-associated genes are bound with other genes that are transcribed to opposite direction. The observations may encourage us to investigate in the molecular mechanisms how DNA repair/mitochondrial function/immune response-associated genes are regulated by bidirectional promoters. Not only protein-coding genes, but also quite a few ncRNAs, which play important roles in various cellular events, are transcribed under the regulation of the bidirectional promoters. More importantly, we know that dysregulation in the promoter activity and transcription initiation of genes might cause human diseases. Review Contributes to the key topic of bi-directional promoters and their role in basic and clinical medicine or pharmaceutical sciences From the Back Cover <p>Recent studies in human genetics and <i>in silico</i> analyses have revealed that a number of genes are head-head orientated with other genes or non-coding RNAs. The expression of regulatory element-containing 5’-upstream regions of gene pairs are referred to as <i>bi-directional promoters</i> and are thought to have a key role in biological regulatory mechanisms.</p> <p>For example, tumor suppressor protein-encoding <i>TP53</i> and <i>BRCA1</i> genes are head-head bound with <i>WRAP53</i> and <i>NBR2</i>, respectively. DNA-repair factor-encoding <i>ATM</i> and <i>PRKDC</i> (<i>DNA-PKcs</i>) genes have bidirectional partner <i>NPAT</i> and <i>MCM4</i>, respectively. Surveillance of the human DNA database has revealed that the numbers of DNA repair/mitochondrial function/immune response-associated genes are bound with other genes that are transcribed to opposite direction. The observations may encourage us to investigate in the molecular mechanisms how DNA repair/mitochondrial function/immune response-associated genes are regulated by bidirectional promoters. Not only protein-coding genes, but also quite a few ncRNAs, which play important roles in various cellular events, are transcribed under the regulation of the bidirectional promoters. More importantly, we know that dysregulation in the promoter activity and transcription initiation of genes might cause human diseases. </p> About the Author Professor Uchiumi received his Bachelor's degree (Chemistry) from Tokyo University of Science in 1987. In 1993, after obtaining his Ph.D. degree (Molecular Biology) from Tokyo University, he joined Professor S. Tanuma's Laboratory at Tokyo University of Science as an Assistant Professor. He obtained his second Ph.D. (Pharmaceutical Science) from Tokyo University of Science in 1999 and in 2000 was promoted to the position of Lecturer at Tokyo University of Science. Professor Uchiumi then went abroad as a post-doctoral researcher for the United States-Japan Cooperative Cancer Research Program in Professor E. Fanning’s Laboratory at Vanderbilt University, 2000-2001. Professor Uchiumi was promoted to Associate Professor and then Full Professor at Tokyo University of Science in 2010 and 2016, respectively. Professor Satoru Miyazaki’s key area of research is genome biology (Bioinformatics, databases).