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