Abstract¡G
TAL1 gene was originally discovered as a result of its activation by chromosome rearrangements in T cell acute lymphoblastic leukaemia(T-ALL). Further studies have shown that TAL1 expression is aberrantly activated by several mechanisms including chromosome translocations, interstitial deletion and transactivation without detectable chromosomal alteration.
TAL1 gene encodes a bHLH transcription factor, that is essential for the development of all haematopoietic lineages and its expression is maintained during differentiation along erythroid, mast and megakaryocytic cell lineages, but not in normal peripheral T-lymphocytes. The bHLH motif of these protein is responsible for DNA binding and dimerization with other bHLH proteins involved in transcription regulation. TAL1 protein is able to form heterodimers with the ubiquitously expressed E2A gene products, E47 and E12, and the heterodimers bind to E-box motif with the general sequence CANNTG. But the target genes for TAL1 oncoprotein have not yet been identified.
We have previously isolated TAL1/E12 heterodimer bound genomic fragments by chromatin immunoprecipitation from K562 cells, and selected 6 fragments with one to four E-box CANNTG sequences. In order to determine if these fragments could be the regulatory elements of potential target genes of TAL1 oncoprotein, we inserted these 6 DNA fragments individually into pGL3 to generate recombinant reporter plasmids. The transfection experiments indicated that K34 and K94 DNA fragments behaved as a transcriptional transactivating sequence, and TAL1 and E12 proteins are required for efficient transcriptional activity. We also showed that transfection of these two recombinant constructs into K562 cells generated positive transcriptional activity, in a level similar to that in TAL1 and E12 co-transfected COS1 cells. These results established that both K34 and K94 DNA fragments are likely to contain a promoter of potential TAL1 target genes.
| Identifer | oai:union.ndltd.org:NSYSU/oai:NSYSU:etd-0118102-110236 |
| Date | 18 January 2002 |
| Creators | Tsao, Su-Hua |
| Contributors | Jiin-Tsuey Cheng, Chung-Lung Cho, Yi-Ren Hong |
| Publisher | NSYSU |
| Source Sets | NSYSU Electronic Thesis and Dissertation Archive |
| Language | Cholon |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0118102-110236 |
| Rights | unrestricted, Copyright information available at source archive |
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