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K Leroy-Viard, MA Vinit, N Lecointe, D Mathieu-Mahul and PH Romeo
INSERM U 91, Hopital Henri Mondor, Creteil, France.
The tal-1 gene, frequently activated in human T-cell acute lymphoblastic
leukemia (T-ALL), is expressed in the erythroid, megakaryocytic, and mast
cell lineages during normal hematopoiesis. To gain further insight into the
molecular mechanisms that control tal-1 expression, we investigated tal-1
chromatin structure in erythroid/megakaryocytic cell lines and in T-cell
lines either with or without tal-1 rearrangements. Tal-1 transcription was
shown to be monoallelic in Jurkat, a T-cell line that expresses tal-1 in
the absence of apparent genomic alteration of the locus. Methylation
studies indicated that the tal-15' GC-rich region behaves like a CpG
island, hypomethylated in normal cells, and methylated de novo on
transcriptionally inactive alleles in established cell lines. Five major
DNase-I hypersensitive sites (HS) were mapped in the tal-1 locus. HS I, IV,
and V were exclusively observed in the erythroid/megakaryocytic cell lines
that express tal-1 from the promoters 1a and 1b. HS II was weak in
hematopoietic cell lines, absent in Hela, and greatly enhanced in Jurkat,
suggesting that this region might be implicated in the cis-activation of
tal-1 promoter 1b in this cell line. HS III was weak in HEL and Jurkat, and
greatly enhanced in DU528, a T-cell line that bears a t (1;14) and
initiates tal-1 transcription within exon 4. These results suggest that
distinct regulatory elements are associated with the use of the different
tal-1 promoters.
This article has been cited by other articles:
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| Copyright © 1994 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
