1: Oncogene. 1998 Sep 3;17(9):1149-57. 

Fli-1b is generated by usage of differential splicing and alternative promoter.

Dhulipala PD, Lee L, Rao VN, Reddy ES.

Department of Human Genetics, Allegheny University of the Health Sciences,
Philadelphia, Pennsylvania 19102, USA.

The proto-oncogene Fli-1, a member of Ets family is rearranged or activated
through proviral integration in erythroleukemias, induced by Friends' Murine
Leukemia Virus. The DNA binding domain (ETS domain) of Fli-1 is fused to the RNA
binding domain of EWS by t(11q24:22q12) chromosomal translocation in Ewing's
sarcoma and primitive neuroectodermal tumors. Screening of human cDNA libraries
has identified two different 5'-termini and alternatively spliced forms of the
human Fli-1 gene (Fli-1b), suggesting the possible existence of two independent
promoters. The genomic sequence adjacent to the alternate exon of human Fli-1b
gene shows functional promoter activity when cloned in promoter-less CAT
expression vector and transfected into QT-6 cells. The transcription initiation
(CAP) site and minimum promoter region necessary for function were localized.
The 5'-flanking regions of human Fli-1b and mouse Fli-1 show 80% homology
suggesting conserved promoter regulatory elements. The Fli-1b 5'-flanking
sequence lacks canonical TATA or CCAAT boxes but contains a partially conserved
TATA-like sequence at position 242. Several transcription factor binding
sequences like ATF/CREB, E2A-PBX1, EBP, PEA-3, ETS-2, Sp-1, c-Myc, TBP, GATA-1
and Oct-3 were conserved in the promoter sequence. Functional promoter assays
revealed that Fli-1b promoter shows very strong transcriptional activation
compared to Fli-1 promoter. We also showed that variant Fli-1b has
transcriptional activation properties similar to those of Fli-1. Fli-1b and
Fli-1 show differential expression in various hematopoietic cell lines. This
differential expression and promoter activities of Fli-1 and Fli-1b suggests
that several mechanisms are involved in Fli-1 gene regulation which are mediated
by many transcription factors.

PMID: 9764825 [PubMed - indexed for MEDLINE]


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