A novel DNMT3B subfamily, DeltaDNMT3B, is the predominant form of DNMT3B in non-small cell lung cancer.
De novo promoter DNA methylation represses gene transcription and is a common mechanism to inactivate tumor suppressor genes in tumorigenesis. DNMT3B plays an important role in de novo DNA methylation. We report here the identification of a novel DNMT3B subfamily, termed DeltaDNMT3B, whose expression is initiated through a promoter located at intron 4 and exon 5 of the DNMT3B gene. At least 7 transcriptional variants of DeltaDNMT3B have been observed as the result of alternative pre-mRNA splicing. Predicted proteins derived from these variants suggest that 4 of the variants share a conservative enzymatic domain but contain a variable PWWP motif, a putative DNA binding structure, whereas 3 of the variants lack the enzymatic domain due to predicted premature translational termination. In non-small cell lung cancer (NSCLC) cell lines, DeltaDNMT3B variants are frequently expressed and are the predominant forms of DNMT3B. Similarly, DeltaDNMT3B variants are frequently expressed in primary NSCLC but are not detectable or are expressed at low levels in corresponding normal lung tissue. Our results indicate that DeltaDNMT3B is the major expression form of DNMT3B in NSCLC and may play an important role in the development of aberrant promoter methylation during lung tumorigenesis.
Wang
Luo
L
Molecular Biology Laboratory, Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, 77030, USA.
Wang
Jie
J
Sun
Shiyong
S
Rodriguez
Marivonne
M
Yue
Ping
P
Jang
Se Jin
SJ
Mao
Li
L
D017398:Alternative Splicing; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology* / Q000235:genetics; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008156:Luciferases / Q000235:genetics; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D014162:Transfection; D000097584:DNA Methyltransferase 3B
D004247:DNA; D004248:DNA (Cytosine-5-)-Methyltransferases; D007527:Isoenzymes; D008156:Luciferases; D012333:RNA, Messenger; D000097584:DNA Methyltransferase 3B