Positive and negative transcriptional control by the TAL1 helix-loop-helix protein.

Abstract

Tumor-specific activation of the TALI gene is the most common genetic defect acted with T-cell acute lymphoblatic leukemia. The TALI gene products possess a basic helix-oop-helix (bHLH)

p300 functions as a transcriptional coactivator for the TAL1/SCL oncoprotein

“…While transactivation was considerably higher with E12 alone, similar to what had been previously reported (Hsu et al, 1994c), cotransfection of Tal1 and E12 expression vectors led to signi®cant activation of a luciferase reporter gene ( Figure 4). Transfection of p300 or a deletion construct lacking the E1A-interacting domain, p300dl10, was found to further increase luciferase gene expression in both Tal1-and E12-transfected HeLa (Figure 4) and NIH3T3 cells (not shown).…”

“…TAL1 has been reported to act as a positive (Hsu et al, 1994c;Ono et al, 1997) and a negative (Hofmann and Cole, 1996;Hsu et al, 1994c;Park and Sun, 1998) regulator of transcription in transient transfection assays. Depending, conceivably, on the speci®c coregulators with which it interacts, it could function physiologically as either an activator or a repressor.…”

“…To that end, electrophoretic mobility shift assays (EMSA) were carried out using extracts from NIH3T3 cells transfected with Tal1 and p300 expression vectors and from Tal1-expressing MEL cells. Although its natural targets have yet to be identi®ed, a preferred DNA-binding sequence was determined for TAL1/E2A heterodimers (Hsu et al, 1994a) that was capable of binding endogenously expressed TAL1 heterodimers (Hsu et al, 1994a) and of directing the transcription of a linked reporter gene (Hsu et al, 1994c). Using this preferred TAL1/E2A binding site as probe, a highly retarded protein-DNA complex was identi®ed with extracts from both transfected NIH3T3 cells (not shown) and DMSOinduced MEL cells (Figure 2).…”

“…The E1bLUC-E6 reporter construct contains six copies of the preferred TAL1/E2A-binding motif 5'-AACAGATGGT-3' (Hsu et al, 1994a) linked to an E1b-TATA-luciferase reporter. This construct was generously provided by Richard Baer (Texas Southwestern Medical Center, Dallas, TX, USA) and, except for the reporter, is identical to E1bCAT-E6 (Hsu et al, 1994c). The (GAL4) 5 E1bCAT reporter contains ®ve GAL4-binding sites upstream of a minimal E1b promoter and CAT gene and was provided by Mark Ptashne (Lillie and Green, 1989).…”

The CD2-scl transgene alters the phenotype and frequency of T-lymphomas in N-ras transgenic or p53 deficient mice

“…In addition to this role in early haemopoiesis, experiments in tissue culture have provided evidence that scl is important at later stages of haemopoiesis for normal erythroid and monocytic lineage commitment and di erentiation (Green et al, 1991;Aplan et al, 1992;Tanigawa et al, 1993). Transcriptional regulation by scl may, in part, be controlled by the presence of scl-binding partners such as E12, E47 (Hsu et al, 1994) and LMO-2 (Valge-Archer et al, 1994;Wadman et al, 1994). However, the downstream target genes have not yet been identi®ed.…”