c-Myc regulates the coordinated transcription of brain disease-related PDCD10-SERPINI1 bidirectional gene pair.
Two brain disease-related genes, one coding for the protease inhibitor SERPINI1 which is down-regulated in brain tumors, and the other for the PDCD10 programmed cell death gene which is often mutated in cerebral cavernous malformation, are closely adjacent in a head-to-head configuration and separated by only 851 bp on human chromosome 3q26. The 851-bp intergenic region contains a GC-rich 175-bp minimal bidirectional promoter which is essential for transcriptional activation of the two flanking genes. The oncogenic c-Myc transcription factor was identified to bind to a non-canonical E-box element (5'-CATGCG-3') of the minimal bidirectional promoter to drive both gene expressions. Methylation at the specific C nucleotide within the E-box sequence (5'-CATG(m)CG-3'), however, would severely interfere with the binding of c-Myc to the E-box. These results suggest that c-Myc plays an important role in regulating the coordinated transcription of the PDCD10-SERPINI1 bidirectional gene pair, and is possibly involved in differential expressions of these two neighboring genes in central nervous system diseases such as brain cancer.
Chen
Ping-Yen
PY
National Institute of Cancer Research, National Health Research Institutes, Zhunan, Miaoli County 35053, Taiwan, ROC.
Chang
Wun-Shaing W
WS
Lai
Yiu-Kay
YK
Wu
Cheng-Wen
CW
D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation / Q000379:methods; D019175:DNA Methylation / Q000187:drug effects; D000077209:Decitabine; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005909:Glioblastoma; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed / Q000379:methods; D009447:Neuroblastoma; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000737:chemistry / Q000378:metabolism*; D015843:Serpins / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology*; D000097522:Neuroserpin
D051017:Apoptosis Regulatory Proteins; D001374:Azacitidine; D000077209:Decitabine; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D009479:Neuropeptides; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D015843:Serpins; D000097522:Neuroserpin; C489427:MYC protein, human; C495390:PDCD10 protein, human