The 5′HS4 core element of the human β-globin locus control region is required for high-level globin gene expression in definitive but not in primitive erythropoiesis 1 1Edited by M. Yaniv

Autor: Qiliang Li, Michael McArthur, George Stamatoyannopoulos, Kenneth R. Peterson, Patrick A. Navas
Rok vydání: 2001
Předmět:
Zdroj: Journal of Molecular Biology. 312:17-26
ISSN: 0022-2836
DOI: 10.1006/jmbi.2001.4939
Popis: To assess the contribution of DNase I-hypersensitive site 4 (HS4) of the beta-globin locus control region (LCR) to overall LCR function we deleted a 280 bp fragment encompassing the core element of 5'HS4 from a 248 kb beta-globin locus yeast artificial chromosome (beta-YAC) and analyzed globin gene expression during development in beta-YAC transgenic mice. Four transgenic 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, deletion 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.
Databáze: OpenAIRE
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