The SCL gene product: a positive regulator of erythroid differentiation.

Abstract

The SCL (tal-l, TCLS) gene is a member of the basic domain, helix-loop-helix (bHLH) class of putative transcription factors. We found that (i) the SCL promoter for exon Ia contains a potential recognition site for GATA-binding transcription factors, (ii) SCL mRNA is expressed in all erythroid tissues and cell lines examined, and (iii) SCL mRNA increases upon induced differentiation of murine erythroleukemia (MEL) cells, and inferred that SCL may play a physiologic role in erythroid differentiation. We used gel shift and transfection assays to demonstrate that the GATA motif in the SCL promoter binds GATA-1 (and GATA-2), and also mediates transcriptional transactivation. To identify a role for SCL in erythroid differentiation, we generated stable transfectants of MEL and K562 (a human chronic myelogenous leukemia cell line that can differentiate along the erythroid pathway) cells overexpressing wildtype, antisense or mutant SCL cDNA. Increasing the level -of SCL expression in two independent MEL lines (F4-6 and C19, a 745 derivative) and K562 cells increased the rate of spontaneous (i.e. in the absence of inducer) erythroid differentiation. Conversely, induced differentiation was inhibited in MEL transfectants expressing either antisense SCL cDNA or a mutant SCL lacking the basic domain. Our experiments suggest that the SCL gene can be a target for the erythroid transcription factor GATA-1 and that the SCL gene product serves as a positive regulator of erythroid differentiation.

Standardization and quality control studies of ‘real-time’ quantitative reverse transcriptase polymerase chain reaction of fusion gene transcripts for residual disease detection in leukemia – A Europe Against Cancer Program

“…The TAL1 protein can heterodimerize with other bHLH transcription factors, including members of the E2A family, and is an essential factor for the development of all hematopoietic lineages. [136][137][138] The SIL gene is a member of the immediateearly gene family, but its function in hematopoietic cells is not yet well defined. 129,139 Although both the SIL and TAL1 genes contain several conserved deletion breakpoints, most cases (X95%) involve the sildb1 breakpoint in combination with the taldb1 or taldb2 breakpoint.…”

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

“…Tal1 expression was found to increase signi®cantly in murine erythroleukemia (MEL) cell lines stimulated to di erentiate with chemical inducers (Aplan et al, 1992;Green et al, 1991), while expression of Tal1 antisense RNA inhibited their di erentiation (Aplan et al, 1992). Further, expression of a full length TAL1 cDNA potentiated erythroid di erentiation of a human leukemia cell line (Hoang et al, 1996) and increased erythroid colony formation by normal human bone marrow cells (Elwood et al, 1998).…”

GOOSECOID inhibits erythrocyte differentiation by competing with Rb for PU.1 binding in murine cells

“…Many transcription factors are thought to play a role in erythropoiesis, such as GATA-1 (Kulessa et al, 1995;Tsai et al, 1991), GATA-2 (Tsai et al, 1994), PU.1 (Hromas et al, 1993;Schuetze et al, 1992Schuetze et al, , 1993 and SCL (Aplan et al, 1992;Begley et al, 1989;Shivdasani and Orkin, 1996). Among these, the role of PU.1 in erythropoiesis is still controversial.…”