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Opposing effects of the basic helix-loop-helix transcription factor SCL on
erythroid and monocytic differentiation
T Hoang, E Paradis, G Brady, F Billia, K Nakahara, NN Iscove and IR Kirsch
Clinical Research Institute of Montreal, Department of Pharmacology,
University of Montreal, Canada.
The SCL gene (also called Tal-1 or TCL5) was identified because of its
association with chromosomal translocations in childhood T-cell lymphoid
leukemias. SCL codes for a basic helix-loop-helix (bHLH) factor that can
function as a transcriptional activator or repressor. In the adult, SCL
expression is restricted to hematopoietic cells and tissues, but its
function in the process of lineage commitment is unknown. The present study
was designed to address the role of SCL in hematopoietic cell
differentiation. SCL expression was determined in primary hematopoietic
cells through the screening of cDNA samples obtained by reverse
transcription-polymerase chain reaction (RT-PCR) from single cells at
different stages of differentiation. SCL RNA expression was highest in
bipotential and committed erythroid precursors and diminished with
subsequent maturation to proerythroblasts and normoblasts. In contrast, SCL
mRNA was low to undetectable in precursors of granulocytes and monocytes
and their maturing progeny. The same pattern of expression was observed
after erythroid or monocytic differentiation of a bipotent cell line, TF-1,
in that SCL mRNA levels remained elevated during erythroid differentiation
and were downregulated with monocytic differentiation. Accordingly, TF-1
was chosen as a model to investigate the functional significance of this
divergent pattern of SCL expression in the two lineages. Four independent
clones stably transfected with an SCL expression vector exhibited enhanced
spontaneous and delta- aminolevulinic acid-induced erythroid
differentiation as measured by glycophorin expression and
hemoglobinization, consistent with the view that SCL is a positive
regulator of erythroid differentiation. Furthermore, constitutive SCL
expression interfered with monocytic differentiation, as assessed by the
generation of adherent cells and the expression of Fc gamma RII in response
to TPA. These results suggest that the downregulation of SCL may be
required for monocytic differentiation.
Volume 87,
Issue 1,
pp. 102-111,
01/01/1996
Copyright © 1996 by The American Society of Hematology
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