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PMID: 8248258 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Germ-line transmission and developmental regulation of a 150-kb yeast artificial chromosome containing the human beta-globin locus in transgenic mice.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 90 ·No. 23 ·1993-12-01 ·Pages 11381-5

Gaensler KM, Kitamura M, Kan YW

Abstract

Sequential expression of the genes of the human beta-globin locus requires the formation of an erythroid-specific chromatin domain spanning > 200 kb. Regulation of this gene family involves both local interactions with proximal cis-acting sequences and long-range interactions with control elements upstream of the locus. To make it possible to analyze the interactions of cis-acting sequences of the human beta-globin locus in their normal spatial and sequence context, we characterized two yeast artificial chromosomes (YACs) 150 and 230 kb in size, containing the entire beta-globin locus. We have now successfully integrated the 150-kb YAC into the germ line of transgenic mice as a single unrearranged fragment that includes the locus control region, structural genes, and 30 kb of 3' flanking sequences present in the native locus. Expression of the transgenic human beta-globin locus is tissue- and developmental stage-specific and closely follows the pattern of expression of the endogenous mouse beta-globin locus. By using homology-directed recombination in yeast and methods for the purification and transfer of YACs into transgenic mice, it will now be feasible to study the physiological role of cis-acting sequences in specifying an erythroid-specific chromatin domain and directing expression of beta-globin genes during ontogeny.

MeSH Terms
Age Factors Animals Base Sequence Chromosomes, Artificial, Yeast Cloning, Molecular DNA Primers/chemistry Erythropoiesis Gene Expression Regulation Globins/genetics Humans Mice Mice, Transgenic Molecular Sequence Data RNA, Messenger/genetics Restriction Mapping Tissue Distribution
Chemicals
DNA Primers RNA, Messenger Globins
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Gaensler K M
Department of Medicine, University of California, San Francisco 94143-0724.
Kitamura M
Kan Y W
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.90.23.11381
Published
1993-12-01
Pages
11381-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC47986
Subset
IM
Grants
NIDDK NIH HHS · DK16666 · United States
NHLBI NIH HHS · HL02711 · United States
External Links
PubMed source DOI: 10.1073/pnas.90.23.11381 PMC Full Text View journal details
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