Germ-line transmission and developmental regulation of a 150-kb yeast artificial chromosome containing the human [beta]-globin locus in transgenic mice
Journal Article
·
· Proceedings of the National Academy of Sciences of the United States of America; (United States)
- Univ. of California, San Francisco, CA (United States)
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, the authors characterized two yeast artificial chromosomes (YACs) 150 and 230 kb in size, containing the entire [beta]-globin locus. They 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[prime] 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.
- OSTI ID:
- 7182574
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America; (United States), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States) Vol. 90:22; ISSN PNASA6; ISSN 0027-8424
- Country of Publication:
- United States
- Language:
- English
Similar Records
Autonomous developmental control of human embryonic globin gene switching in transgenic mice
Two 3' sequences direct adult erythroid-specific expression of human. beta. -globin genes in transgenic mice
High-level. beta. -globin expression after retroviral transfer of locus activation region-containing human. beta. -globin gene derivatives into murine erythroleukemia cells
Journal Article
·
Thu Nov 22 23:00:00 EST 1990
· Science (Washington, D.C.); (USA)
·
OSTI ID:5948591
Two 3' sequences direct adult erythroid-specific expression of human. beta. -globin genes in transgenic mice
Journal Article
·
Thu Oct 01 00:00:00 EDT 1987
· Proc. Natl. Acad. Sci. U.S.A.; (United States)
·
OSTI ID:7027177
High-level. beta. -globin expression after retroviral transfer of locus activation region-containing human. beta. -globin gene derivatives into murine erythroleukemia cells
Journal Article
·
Tue May 01 00:00:00 EDT 1990
· Proceedings of the National Academy of Sciences of the United States of America; (United States)
·
OSTI ID:5323125