DOI: 10.1182/blood.v90.11.4602. The Human β Globin Locus Introduced by YAC Transfer Exhibits a Specific and Reproducible Pattern of Developmental Regulation in Transgenic Mice

The Human β Globin Locus Introduced by YAC Transfer Exhibits a Specific and Reproducible Pattern of Developmental Regulation in Transgenic Mice

10.1182/blood.v90.11.4602

Crossref journal-article

American Society of Hematology

Blood (234)

Abstract

Abstract The human β globin locus spans an 80-kb chromosomal region encompassing both the five expressed globin genes and the cis-acting elements that direct their stage-specific expression during ontogeny. Sequences proximal to the genes and in the locus control region, 60 kb upstream of the adult β globin gene, are required for developmental regulation. Transgenic studies have shown that altering the structural organization of the locus disrupts the normal pattern of globin gene regulation. Procedures for introducing yeast artificial chromosomes (YACs) containing large genetic loci now make it possible to define the sequences required for stage-restricted gene expression in constructs that preserve the integrity of the β globin locus. We demonstrate that independent YAC transgenic lines exhibit remarkably similar patterns of globin gene expression during development. The switch from γ to β globin predominant expression occurs between day 11.5 and 12.5 of gestation, with no more than twofold differences in human β globin mRNA levels between lines. Human β globin mRNA levels were twofold to fourfold lower than that of mouse βmaj, revealing potentially significant differences in the regulatory sequences of the two loci. These findings provide an important basis for studying regulatory elements within the β globin locus.

Bibliography

Porcu, S., Kitamura, M., Witkowska, E., Zhang, Z., Mutero, A., Lin, C., Chang, J., & Gaensler, K. M. L. (1997). The Human Î² Globin Locus Introduced by YAC Transfer Exhibits a Specific and Reproducible Pattern of Developmental Regulation in Transgenic Mice. Blood, 90(11), 4602â4609.

Authors 8

Susanna Porcu (first)
Michael Kitamura (additional)
Ewa Witkowska (additional)
Zemin Zhang (additional)
Annick Mutero (additional)
Chin Lin (additional)
Judy Chang (additional)
Karin M.L. Gaensler (additional)

References 33 Referenced 69

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10.1002/j.1460-2075.1990.tb08100.x / EMBO J / Definition of the minimal requirements within the human beta-globin gene and the dominant control region for high level expression. by Collis (1990)
10.1093/nar/18.12.3503 / Nucleic Acids Res / DNAse 1 hypersensitive sites 1, 2, and 3 of the human b-globin dominant control region direct position-independent expression. by Fraser (1990)
10.1016/0092-8674(87)90584-8 / Cell / Position-independent, high-level expression of the human beta-globin gene in transgenic mice. by Grosveld (1987)
10.1073/pnas.86.18.7033 / Proc Natl Acad Sci USA / The human beta-globin locus activation region alters the developmental fate of a human fetal globin gene in transgenic mice. by Enver (1989)
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10.1016/0888-7543(91)90188-K / Genomics / Physical mapping of yeast artificial chromosomes containing sequences from the human b globin gene region. by Gaensler (1991)
10.1073/pnas.90.23.11381 / Proc Natl Acad Sci USA / Germline transmission and developmental regulation of a 150 kb YAC containing the human b globin locus in transgenic mice. by Gaensler (1993)
{'key': '2019112005530112600_B16'}
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{'key': '2019112005530112600_B29'}
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Dates

Type	When
Created	5 years, 10 months ago (Oct. 14, 2019, 4:09 a.m.)
Deposited	5 years, 9 months ago (Nov. 20, 2019, 5:58 a.m.)
Indexed	3 months, 3 weeks ago (May 1, 2025, 12:27 a.m.)
Issued	27 years, 8 months ago (Dec. 1, 1997)
Published	27 years, 8 months ago (Dec. 1, 1997)
Published Print	27 years, 8 months ago (Dec. 1, 1997)

Funders 0

None

BibTeX

@article{Porcu_1997, title={The Human β Globin Locus Introduced by YAC Transfer Exhibits a Specific and Reproducible Pattern of Developmental Regulation in Transgenic Mice}, volume={90}, ISSN={0006-4971}, url={http://dx.doi.org/10.1182/blood.v90.11.4602}, DOI={10.1182/blood.v90.11.4602}, number={11}, journal={Blood}, publisher={American Society of Hematology}, author={Porcu, Susanna and Kitamura, Michael and Witkowska, Ewa and Zhang, Zemin and Mutero, Annick and Lin, Chin and Chang, Judy and Gaensler, Karin M.L.}, year={1997}, month=dec, pages={4602–4609} }

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