NDLI: Embryonic and fetal β-globin gene repression by the orphan nuclear receptors, TR2 and TR4

Content Provider	PubMed Central
Author	Tanabe, Osamu Mcphee, David Kobayashi, Shoko Shen, Yannan Brandt, William Jiang, Xia Campbell, Andrew D. Chen, Yei-tsung Chang, Chawn Shang Yamamoto, Masayuki Tanimoto, Keiji Engel, James Douglas
Copyright Year	2007
Abstract	The TR2 and TR4 orphan nuclear receptors comprise the DNA-binding core of direct repeat erythroid definitive, a protein complex that binds to direct repeat elements in the embryonic and fetal β-type globin gene promoters. Silencing of both the embryonic and fetal β-type globin genes is delayed in definitive erythroid cells of Tr2 and Tr4 null mutant mice, whereas in transgenic mice that express dominant-negative TR4 (dnTR4), human embryonic ɛ-globin is activated in primitive and definitive erythroid cells. In contrast, human fetal γ-globin is activated by dnTR4 only in definitive, but not in primitive, erythroid cells, implicating TR2/TR4 as a stage-selective repressor. Forced expression of wild-type TR2 and TR4 leads to precocious repression of ɛ-globin, but in contrast to induction of γ-globin in definitive erythroid cells. These temporally specific, gene-selective alterations in ɛ- and γ-globin gene expression by gain and loss of TR2/TR4 function provide the first genetic evidence for a role for these nuclear receptors in sequential, gene-autonomous silencing of the ɛ- and γ-globin genes during development, and suggest that their differential utilization controls stage-specific repression of the human ɛ- and γ-globin genes.
Related Links	http://dx.doi.org/10.1038/sj.emboj.7601676
Starting Page	2295
File Format	PDF
ISSN	14602075
e-ISSN	14602075
Journal	The EMBO Journal
Issue Number	9
Volume Number	26
Language	English
Publisher	Nature Publishing Group
Publisher Date	2007-05-02
Access Restriction	Open
Rights Holder	Nature Publishing Group
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Neuroscience Immunology and Microbiology Medicine Molecular Biology

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