TY - JOUR
TI - An embryonic-specific repressor element located 3 ` to the
(A)gamma-globin gene influences transcription of the human beta-globin
locus in transgenic mice
AU - Katsantoni, EZ
AU - de Krom, M
AU - Kong-a-San, J
AU - Imam, AMA and
AU - Grosveld, F
AU - Anagnou, NP
AU - Strouboulis, J
JO - Experimental Hematology and Oncology
PY - 2004
VL - 32
TODO - 2
SP - 224-233
PB - EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
SN - null
TODO - 10.1016/j.exphem.2003.11.001
TODO - null
TODO - Objective. Persistent expression of the human fetal gamma-globin genes
in the adult stage is often associated with naturally occurring
deletions in the human beta-globin locus. The mapping of the 5’
breakpoints of these deletions within the (A)gamma- to delta-globin
intergenic region has suggested that regulatory elements involved in the
silencing of the gamma-globin genes in the adult may be present. We
previously identified two elements in this region, termed Enh and F,
located 3’ to the (A)gamma-globin gene acting as silencers in transient
transfection assays. Here, we tested directly the in vivo significance
of these elements in the developmental regulation of the human beta-like
globin genes. Materials and
Methods. We selectively deleted both Enh and F elements in the context
of a 185-kb human beta-globin locus PAC (P1 phage artificial chromosome)
and tested the effects of this deletion on the expression of the human
beta-like globin genes in transgenic mice.
Results. The Enh/F deletion resulted in an increase in epsilon- and
gamma-globin mRNA levels in the embryonic yolk sac stage of
erythropoiesis, which appears to be due to an increase in the rate of
transcription rather than to an increase in the number of cells
transcribing the human globin locus. However, the human developmental
switching from fetal gamma-globin to adult beta-globin gene expression
in transgenic mice was not affected by this deletion.
Conclusion. These results identify Enh and F as locus-wide regulatory
elements capable of down-regulating transcription of the human
beta-globin locus in an embryonic-specific manner. (C) 2004
International Society for Experimental Hematology. Published by Elsevier
Inc.
ER -