ABSTRACT
The human RNA methyltransferase like 1 gene (RNMTL1) is one of thirteen newly discovered genes within a 116 Kb segment of the chromosome 17p13.3 that suffers from a high frequent loss of heterozygosity in human hepatocellular carcinoma in China1, 2, 3, 4, 5. To understand the molecular mechanisms underlying transcription control of the RNMTL1 gene in human cancers, we decline using of the conventional approach where the cis-elements bound by the known transcription factors are primary targets, and carried out the systematic analyses to dissect the promoter structure and identify/characterize the key cis-elements that are responsible for its strong expression in cell. The molecular approaches applied included 1, the primer extension for mapping of the transcription starts; 2, the transient transfection/reporter assays on a large number of deletion and site-specific mutants of the promoter segment for defining the minimal promoter and the crucial elements within; and 3, the electrophoresis mobility shift assay with specific antibodies for reconfirming the nature of the transcription factors and their cognate cis-elements. We have shown that the interaction of an ATF/CREB element (−38 to −31) and its cognate transcription factors play a predominant role in the promoter activity of the RNMTL1 gene. The secondary DNA structures of the ATF/CREB element play a more vital role in the protein-DNA interaction. Finally, we reported a novel mechanism underlying the YY1 mediated transcription repression, namely, the ATF/CREB dependent transcription-repression by YY1 is executed in absence of its own sequence-specific binding.
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Abbreviations
- LOH:
-
loss of heterozygosity
- HCC:
-
hepatocellular carcinoma
- RNMTL1:
-
RNA methyltransferase like 1
- ATF:
-
activating transcription factor
- CREB:
-
cAMP-response element binding protein
- AP-2:
-
activating protein 2
- YY1:
-
Yin Yang-1
- RT-PCR:
-
reverse transcription-PCR
- VNTR:
-
variable number of repeat
- STR:
-
short tandem repeat
- SNP:
-
single nucleotide polymorphism
- Py:
-
pyrimidine
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Acknowledgements
This work is supported by the 973 projects of China (G1998051004) to Jingde Zhu and (G1998051200) to Dafang Wan, respectively. Thanks are due to Hongyu Zhang and other members in Jingde Zhu's lab for assistance and helps on numerous occasions.
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XU, J., ZHU, J., NI, M. et al. The ATF/CREB site is the key element for transcription of the human RNA methyltransferase like 1 (RNMTL1) gene, a newly discovered 17p13.3 gene. Cell Res 12, 177–197 (2002). https://doi.org/10.1038/sj.cr.7290124
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DOI: https://doi.org/10.1038/sj.cr.7290124
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