M. Kamoun et al., ANALYSIS OF CD2 AND TCR-BETA GENE-EXPRESSION IN JURKAT CELL MUTANTS SUGGESTS A CIS REGULATION OF GENE-TRANSCRIPTION, The Journal of immunology, 155(8), 1995, pp. 3929-3937
Thirty CD2(-) J32 stable clones, derived by mutagenesis and subsequent
immunoselection with anti-CD2 Ab, were used to study the regulation o
f CD2 and TCR gene expression. Analysis of RNA expression revealed tha
t the loss of surface expression of CD2 was due to a lack of expressio
n of CD2 mRNA and was associated with a lack of expression of VDJ TCR-
beta transcripts in 12 of these mutants, sparing the expression of DJ
TCR-beta, TCR-alpha, CD3 gamma, delta, epsilon, and zeta RNA. The expr
ession of other differentiation molecules was unaffected, except for C
D1, CD4, and CD5, which were either decreased or absent in most of the
se mutants. A gain in the expression of TCR-gamma transcripts was obse
rved in each of these mutants, while, as expected, no TCR-gamma transc
ripts were detected in wild-type J32 cells. Several. mutants were able
to use the human CD2 enhancer and the murine TCR-beta enhancer and pr
omoter to activate transcription from reporter genes in the context of
heterologous promoters, indicating that the mutation(s) does not affe
ct transcription pathways. Consistent with this finding is the adequat
e expression in these mutants of several lineage-specific transcriptio
n factors. The expression of CD2 in several of these mutants was rescu
ed by gene transfer using a genomic 28.5-kb CD2 fragment, suggesting t
hat the enhancer function of this gene may be dependent on the enhance
r site. These observations suggest that the-coordinate expressions of
CD2 and TCR-beta genes share common regulatory mechanisms involving fa
ctors regulating chromatin structure and accessibility.