Deletions within the mouse β-globin locus control region preferentially reduce β(min) globin gene expression

Raouf Alami; M. A. Bender; Yong Qing Feng; Steven N. Fiering; Bruce A. Hug; Timothy J. Ley; Mark Groudine; Eric E. Bouhassira

doi:10.1006/geno.1999.6104

Deletions within the mouse β-globin locus control region preferentially reduce β(min) globin gene expression

Raouf Alami, M. A. Bender, Yong Qing Feng, Steven N. Fiering, Bruce A. Hug, Timothy J. Ley, Mark Groudine, Eric E. Bouhassira

Cell Biology

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Abstract

The mouse β-globin gene cluster is regulated, at least in part, by a locus control region (LCR) composed of several developmentally stable DNase I hypersensitive sites located upstream of the genes. In this report, we examine the level of expression of the β(min) and β(maj) genes in adult mice in which HS2, HS3, or HS5,6 has been either deleted or replaced by a selectable marker via homologous recombination in ES cells. Primer extension analysis of RNA extracted from circulating reticulocytes and HPLC analysis of globin chains from peripheral red blood cells revealed that all mutations that reduce the overall output of the locus preferentially decrease β(min) expression over β(maj). The implications of these findings for the mechanism by which the LCR controls expression of the β(maj) and β(min) promoters are discussed. (C) 2000 Academic Press.

Original language	English (US)
Pages (from-to)	417-424
Number of pages	8
Journal	Genomics
Volume	63
Issue number	3
DOIs	https://doi.org/10.1006/geno.1999.6104
State	Published - Feb 1 2000

ASJC Scopus subject areas

Genetics

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title = "Deletions within the mouse β-globin locus control region preferentially reduce β(min) globin gene expression",

abstract = "The mouse β-globin gene cluster is regulated, at least in part, by a locus control region (LCR) composed of several developmentally stable DNase I hypersensitive sites located upstream of the genes. In this report, we examine the level of expression of the β(min) and β(maj) genes in adult mice in which HS2, HS3, or HS5,6 has been either deleted or replaced by a selectable marker via homologous recombination in ES cells. Primer extension analysis of RNA extracted from circulating reticulocytes and HPLC analysis of globin chains from peripheral red blood cells revealed that all mutations that reduce the overall output of the locus preferentially decrease β(min) expression over β(maj). The implications of these findings for the mechanism by which the LCR controls expression of the β(maj) and β(min) promoters are discussed. (C) 2000 Academic Press.",

author = "Raouf Alami and Bender, {M. A.} and Feng, {Yong Qing} and Fiering, {Steven N.} and Hug, {Bruce A.} and Ley, {Timothy J.} and Mark Groudine and Bouhassira, {Eric E.}",

note = "Funding Information: We thank Dr. Ronald L. Nagel for his ongoing support and E. Klein-Bouhassira for spell-checking the manuscript. This work was supported by Grants NIH HL38655 and HL 554350 (E.E.B.), DK52854 and DK44746 (M.G.), and P30 HD28834, through the University of Washington Child Health Research Center (M.A.B.), by NIH DK38362 (T.J.L.), and by Burroughs-Wellcome Career Development Award (S.N.F.). R.A. is supported by Grant NIH HL07556. M.A.B. is a Howard Hughes Medical Institute Physician Postdoctoral Fellow.",

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AU - Hug, Bruce A.

AU - Ley, Timothy J.

AU - Groudine, Mark

AU - Bouhassira, Eric E.

N1 - Funding Information: We thank Dr. Ronald L. Nagel for his ongoing support and E. Klein-Bouhassira for spell-checking the manuscript. This work was supported by Grants NIH HL38655 and HL 554350 (E.E.B.), DK52854 and DK44746 (M.G.), and P30 HD28834, through the University of Washington Child Health Research Center (M.A.B.), by NIH DK38362 (T.J.L.), and by Burroughs-Wellcome Career Development Award (S.N.F.). R.A. is supported by Grant NIH HL07556. M.A.B. is a Howard Hughes Medical Institute Physician Postdoctoral Fellow.

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N2 - The mouse β-globin gene cluster is regulated, at least in part, by a locus control region (LCR) composed of several developmentally stable DNase I hypersensitive sites located upstream of the genes. In this report, we examine the level of expression of the β(min) and β(maj) genes in adult mice in which HS2, HS3, or HS5,6 has been either deleted or replaced by a selectable marker via homologous recombination in ES cells. Primer extension analysis of RNA extracted from circulating reticulocytes and HPLC analysis of globin chains from peripheral red blood cells revealed that all mutations that reduce the overall output of the locus preferentially decrease β(min) expression over β(maj). The implications of these findings for the mechanism by which the LCR controls expression of the β(maj) and β(min) promoters are discussed. (C) 2000 Academic Press.

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Deletions within the mouse β-globin locus control region preferentially reduce β(min) globin gene expression

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