Developmental Control of Gene Expression 
Lineage- and Stage-Specific Expression of 
the mb-1 Gene 
To gain insight into the molecular basis for the 
coordinate lineage-specificity and distinct stage- 
specificities of genes that are expressed only in 
lymphocytes, we extended our studies to the reg- 
ulation of the mb-1 gene. This gene is expressed 
specifically in early-stage B cells. Isolation and 
characterization of the mb l promoter indicated 
that a relatively short DNA fragment contains the 
information for both lineage- and stage-specific- 
ity. The mb-1 promoter was found to contain a 
binding site for a novel B cell-specific factor that 
is present only in nuclear extracts from early- 
stage B cells, thus paralleling the expression pat- 
tern of the mb l gene. 
Isolation and Characterization of 
Lymphoid-Specific cDNA Clones 
To identify a set of new markers for individual 
stages of the lymphocyte lineage and to find gene 
products that are important for the lymphoid cell 
differentiation pathway, our laboratory isolated 
novel lymphocyte-specific cDNA clones by dif- 
ferential screening of a pre-B cell cDNA library 
with cDNA from an erythroid cell line. To iden- 
tify candidate transcriptional regulators among 
the isolated lymphoid-specific cDNAs, we as- 
sayed proteins expressed from the cDNAs in vitro 
for binding to DNA cellulose. 
One of the cDNA clones, which was expressed 
specifically in pre-B and T cell lines, was found 
to encode a 44-kDa protein that binds to DNA 
cellulose. Analysis of the nucleotide sequence of 
this cDNA revealed a homology to the nonhistone 
high-mobility group 1 (HMGl) gene and to ge- 
netically defined regulators of cell specifica- 
tions that include fungal mating-type genes and 
the putative mammalian testis-determining factor 
gene SRY. 
This lymphoid-specific cDNA clone represents 
a gene, termed LEF- 1 {lymphoid enhancer-bind- 
ing factor 1) , that is developmentally regulated 
and expressed in T and pre-B lymphocytes but not 
in later stage B cells or nonlymphoid tissues. 
LEF-1 encodes a nuclear protein with a single 
HMG box that was shown to bind to a functionally 
important site in the T cell antigen receptor 
(TCR) a enhancer. Maximal TCRa enhancer activ- 
ity was found to parallel the cell type-specific 
expression pattern of LEF-1. Moreover, forced 
expression of recombinant LEF- 1 in late-stage B 
cells increases TCRa enhancer function. Taken 
together, these data suggest that LEF- 7 is a regula- 
tory participant in lymphocyte gene expression 
and differentiation. 
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