TY - JOUR
T1 - c-Myc regulates the coordinated transcription of brain disease-related PDCD10-SERPINI1 bidirectional gene pair
AU - Chen, Ping Yen
AU - Chang, Wun Shaing W.
AU - Lai, Yiu Kay
AU - Wu Lee, Cheng-Wen
PY - 2009/8
Y1 - 2009/8
N2 - 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′-CATGmCG-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.
AB - 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′-CATGmCG-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.
UR - http://www.scopus.com/inward/record.url?scp=67651122900&partnerID=8YFLogxK
U2 - 10.1016/j.mcn.2009.05.001
DO - 10.1016/j.mcn.2009.05.001
M3 - Article
C2 - 19442737
AN - SCOPUS:67651122900
SN - 1044-7431
VL - 42
SP - 23
EP - 32
JO - Molecular and Cellular Neuroscience
JF - Molecular and Cellular Neuroscience
IS - 1
ER -