Transcriptional regulation of bidirectional promoters: role of NF-Y
TEKU, GABRIEL (2010)
TEKU, GABRIEL
2010
Bioinformatiikka - Bioinformatics
Lääketieteellinen tiedekunta - Faculty of Medicine
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Hyväksymispäivämäärä
2010-04-01
Julkaisun pysyvä osoite on
https://urn.fi/urn:nbn:fi:uta-1-20438
https://urn.fi/urn:nbn:fi:uta-1-20438
Tiivistelmä
ABSTRACT
BACKGROUND: About 11% of human genes occur in divergent pairs such that both genes are located on opposite strands of DNA, and their immediate promoters are overlapping. The overlapping proximal promoter of both genes form an intergenic region called a bidirectional promoter which is less than 1000 base pairs in length. There is evidence that some cis-regulatory elements in bidirectional promoters control the transcription of both flanking genes. CCAAT boxes are one of the most abundant cis-regulatory elements in the human genome. NF-Y, a heterotrimeric transcription factor, activates CCAAT boxes and requires both the CCAAT box and specific flanking nucleotides for DNA binding.
RESULTS: Using sequence analysis approach, data on the incidence of the NF-Y type CCAAT boxes in bidirectional promoters of both human and mouse genomes was used to deduce the functional and biological significance of NF-Y factor in the transcription mechanism of bidirectional gene pairs. In this study, four major findings were made. Firstly, a considerable number of bidirectional promoters consisted of at least an NF-Y type CCAAT box. This shows a critical role of NF-Y in the underlying bidirectional promoter regulation mechanism. Secondly, forward and reverse orientation of NF-Y type CCAAT boxes occurred in similar proportions in both bidirectional and unidirectional promoters, demonstrating NF-Y's ability to bind its recognition sequence in either orientation. Thirdly, a considerable number of NF-Y type CCAAT boxes were found in their functional position in bidirectional promoters, associating NF-Y to the recruitment of the transcription machinery. Lastly, NF-Y type CCAAT boxes were also significantly distributed further upstream to their functional position, suggesting that NF-Y is potentially connected to transactivating bidirectional promoters.
CONCLUSION: These results are in support of NF-Y's essential role in the general and activated transcriptional regulation of bidirectional gene pairs. This work provides an important contribution in understanding the regulatory mechanism of bidirectional promoters and, in turn, their subsequent biomedical applications.
Asiasanat:divergent genes, bidirectional promoters, NF-Y, CCAAT box, bidirectional gene pair, head-to-head genes, transcription, regulation
BACKGROUND: About 11% of human genes occur in divergent pairs such that both genes are located on opposite strands of DNA, and their immediate promoters are overlapping. The overlapping proximal promoter of both genes form an intergenic region called a bidirectional promoter which is less than 1000 base pairs in length. There is evidence that some cis-regulatory elements in bidirectional promoters control the transcription of both flanking genes. CCAAT boxes are one of the most abundant cis-regulatory elements in the human genome. NF-Y, a heterotrimeric transcription factor, activates CCAAT boxes and requires both the CCAAT box and specific flanking nucleotides for DNA binding.
RESULTS: Using sequence analysis approach, data on the incidence of the NF-Y type CCAAT boxes in bidirectional promoters of both human and mouse genomes was used to deduce the functional and biological significance of NF-Y factor in the transcription mechanism of bidirectional gene pairs. In this study, four major findings were made. Firstly, a considerable number of bidirectional promoters consisted of at least an NF-Y type CCAAT box. This shows a critical role of NF-Y in the underlying bidirectional promoter regulation mechanism. Secondly, forward and reverse orientation of NF-Y type CCAAT boxes occurred in similar proportions in both bidirectional and unidirectional promoters, demonstrating NF-Y's ability to bind its recognition sequence in either orientation. Thirdly, a considerable number of NF-Y type CCAAT boxes were found in their functional position in bidirectional promoters, associating NF-Y to the recruitment of the transcription machinery. Lastly, NF-Y type CCAAT boxes were also significantly distributed further upstream to their functional position, suggesting that NF-Y is potentially connected to transactivating bidirectional promoters.
CONCLUSION: These results are in support of NF-Y's essential role in the general and activated transcriptional regulation of bidirectional gene pairs. This work provides an important contribution in understanding the regulatory mechanism of bidirectional promoters and, in turn, their subsequent biomedical applications.
Asiasanat:divergent genes, bidirectional promoters, NF-Y, CCAAT box, bidirectional gene pair, head-to-head genes, transcription, regulation