The 5 ' HS4 core element of the human beta-globin locus control region is required for high-level globin gene expression in definitive but not in primitive erythropoiesis
Pa. Navas et al., The 5 ' HS4 core element of the human beta-globin locus control region is required for high-level globin gene expression in definitive but not in primitive erythropoiesis, J MOL BIOL, 312(1), 2001, pp. 17-26
To assess the contribution of DNase I-hypersensitive site 4 (HS4) of the be
ta -globin locus control region (LCR) to overall LCR function we deleted a
280 by fragment encompassing the core element of 5'HS4 from a 248 kb beta -
globin locus yeast artificial chromosome (beta -YAC) and analyzed globin ge
ne expression during development in beta -YAC transgenic mice. Four transge
nic lines were established; each contained at least one intact copy of the
beta -globin locus. The deletion of the 5'HS4 core element had no effect on
globin gene expression during embryonic erythropoiesis. In contrast, delet
ion of the 5'HS4 core resulted in a significant decrease of gamma and beta
-globin gene expression during definitive erythropoiesis in the fetal liver
and a decrease of beta -globin gene expression in adult blood. We conclude
that the core element of 5'HS4 is required for globin gene expression only
in definitive erythropoiesis. Absence of the core element of HS4 may limit
the ability of the LCR to provide an open chromatin domain and/or enhance
gamma and beta -globin gene expression in the adult erythroid cells. (C) 20
01 Academic Press.