title: All of the human beta-type globin genes compete for LCR enhancer activity in embryonic erythroid cells of yeast artificial chromosome transgenic mice.
abstract: In primitive erythroid cells of human beta-globin locus transgenic mice (TgM), the locus control region (LCR)-proximal epsilon- and gamma-globin genes are transcribed, whereas the distal delta- and beta-globin genes are silent. It is generally accepted that the beta-globin gene is competitively suppressed by gamma-globin gene expression at this developmental stage. Previously, however, we observed that epsilon-globin gene expression was severely attenuated when its distance from the LCR was extended, implying that beta-globin gene might also be silenced because of its great distance from the LCR. Here, to clarify the beta-globin gene silencing mechanism, we established TgM lines carrying either gamma- or epsilon- plus gamma-globin promoter deletions, without significantly altering the distance between the beta-globin gene and the LCR. Precocious expression of delta- and beta-globin genes was observed in primitive erythroid cells of mutant, but not wild-type TgM, which was most evident when both the epsilon and gamma promoters were deleted. Thus, we clearly demonstrated that the repression of the delta- and beta-globin genes in primitive erythroid cells is dominated by competitive silencing by the epsilon- and gamma-globin gene promoters, and that epsilon- and the other beta-like globin genes might be activated by two distinct mechanisms by the LCR.
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8577, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Okamura
authors.forename: Hitomi
authors.initials: H
authors.lastname: Matsuzaki
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Campbell
authors.forename: James Douglas
authors.initials: JD
authors.lastname: Engel
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Fukamizu
authors.forename: Keiji
authors.initials: K
authors.lastname: Tanimoto
mesh_terms: D000818:Animals; D018244:Chromosomes, Artificial, Yeast / Q000235:genetics*; D041905:Erythroid Cells / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D019901:Locus Control Region / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D012441:Saccharomyces cerevisiae; D055544:beta-Globins / Q000235:genetics*
chemical_list: D055544:beta-Globins
references.citation: Mol Cell. 2005 Feb 4;17(3):453-62
references.pmid: 15694345
references.citation: Genes Dev. 1991 Aug;5(8):1387-94
references.pmid: 1714415
references.citation: Genes Dev. 1997 Oct 1;11(19):2494-509
references.pmid: 9334315
references.citation: Mol Cell Biol. 2007 Aug;27(16):5664-72
references.pmid: 17548470
references.citation: Mol Cell. 2002 Dec;10(6):1453-65
references.pmid: 12504019
references.citation: Nucleic Acids Res. 2007;35(16):5532-44
references.pmid: 17704132
references.citation: Mol Cell Biol. 2001 Oct;21(19):6507-14
references.pmid: 11533239
references.citation: Blood. 2007 Mar 1;109(5):2210-6
references.pmid: 17077320
references.citation: J Exp Biol. 1998 Apr;201(Pt 8):1099-117
references.pmid: 9510523
references.citation: Nature. 1999 Mar 25;398(6725):344-8
references.pmid: 10192336
references.citation: Nature. 1990 Mar 22;344(6264):309-13
references.pmid: 2314472
references.citation: Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11381-5
references.pmid: 8248258
references.citation: Nat Genet. 1998 Dec;20(4):353-7
references.pmid: 9843206
references.citation: Cell. 1987 Dec 24;51(6):975-85
references.pmid: 3690667
references.citation: Mol Cell Biol. 2006 Jul;26(13):4775-81
references.pmid: 16782867
references.citation: Exp Hematol. 2005 Mar;33(3):259-71
references.pmid: 15730849
references.citation: Genes Dev. 2000 Nov 1;14(21):2778-94
references.pmid: 11069894
references.citation: Proc Natl Acad Sci U S A. 1985 Oct;82(19):6384-8
references.pmid: 3879975
references.citation: Genomics. 1988 Apr;2(3):240-8
references.pmid: 3397061
references.citation: Science. 1998 Jul 3;281(5373):60-3
references.pmid: 9679020
references.citation: Genes Dev. 1999 Oct 1;13(19):2465-77
references.pmid: 10521391
references.citation: Blood. 2002 Nov 1;100(9):3077-86
references.pmid: 12384402
references.citation: Cell. 2000 Mar 3;100(5):499-502
references.pmid: 10721987
references.citation: Mol Cell Biol. 2003 Dec;23(24):8946-52
references.pmid: 14645507
references.citation: Nat Genet. 2003 Oct;35(2):190-4
references.pmid: 14517543
references.citation: Blood. 2006 Feb 15;107(4):1665-72
references.pmid: 16263786
references.citation: Mol Cell. 1997 Dec;1(1):131-9
references.pmid: 9659910
references.citation: Genes Dev. 1990 Mar;4(3):380-9
references.pmid: 1692558
references.citation: Science. 1990 Nov 23;250(4984):1147-9
references.pmid: 2251502
references.citation: Nucleic Acids Res. 1999 Aug 1;27(15):3130-7
references.pmid: 10454609
references.citation: Science. 2002 Feb 15;295(5558):1306-11
references.pmid: 11847345
references.citation: Nat Genet. 2002 Dec;32(4):623-6
references.pmid: 12426570
references.citation: Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11219-23
references.pmid: 1454801
references.citation: Genes Dev. 1995 Dec 15;9(24):3083-96
references.pmid: 8543153