Cloning and characterization of the SIL promoter.
The SIL gene undergoes a site-specific rearrangement with the SCL gene in 25% of patients with T cell acute lymphoblastic leukemia (ALL). The functional result of this rearrangement is that the SIL regulatory elements aberrantly drive expression of the SCL gene. We have cloned and sequenced the human SIL promoter, cloned a murine homolog, found the sequence to be highly conserved, and defined a minimal promoter region. Both the cloned murine and human sequences were found to be highly active in either human or murine cells. SCL mRNA, driven by a cloned SIL promoter, could be downregulated by DMSO in stably transfected F4-6 murine erythroleukemia cells. The SIL promoter was found to be partially unmethylated in proliferating tissues, in which it is highly expressed, and more highly methylated in post-mitotic tissues, in which SIL is not expressed. The isolation of the SIL promoter provides an important tool for the study of both the SIL gene expression as well as the role of the SIL promoter in leukemogenesis.
Colaizzo-Anas
Tina
T
Buffalo State-SUNY, 210 Caudell Hall, Buffalo, NY 14222, USA. tcolaizzo@aol.com
Aplan
Peter D
PD
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D002478:Cells, Cultured; D003001:Cloning, Molecular; D019175:DNA Methylation; D018076:DNA, Complementary / Q000096:biosynthesis / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D004121:Dimethyl Sulfoxide; D005786:Gene Expression Regulation / Q000187:drug effects; D015321:Gene Rearrangement; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D019169:Jurkat Cells; D051379:Mice; D008969:Molecular Sequence Data; D015514:Oncogene Proteins, Fusion; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014176:Protein Biosynthesis; D011506:Proteins / Q000737:chemistry / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D016415:Sequence Alignment; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D013601:T-Lymphocytes / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection
D051792:Basic Helix-Loop-Helix Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D004121:Dimethyl Sulfoxide; D047908:Intracellular Signaling Peptides and Proteins; D015514:Oncogene Proteins, Fusion; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; C103486:SIL protein, mouse; C071236:STIL protein, human; C489366:Tal1 protein, mouse; C067143:TAL1 protein, human