Journal
MOLECULAR CELL
Volume 5, Issue 2, Pages 387-393Publisher
CELL PRESS
DOI: 10.1016/S1097-2765(00)80433-5
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Funding
- NICHD NIH HHS [P30 HD28834] Funding Source: Medline
- NIDDK NIH HHS [DK44746, DK54071] Funding Source: Medline
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We have generated mice with a targeted deletion of the P-globin locus control region (LCR). Mice homozygous for the deletion die early in embryogenesis but can be rescued with a YAC containing the human P-globin locus. After germline passage, deletion of the LCR leads to a severe reduction in expression of all mouse P-like globin genes, but no alteration in the developmental specificity of expression. Furthermore, a DNase I-sensitive open chromatin conformation of the locus is established and maintained. Thus, the dominant role of the LCR in the native locus is to confer high-level transcription, and elements elsewhere in the locus are sufficient to establish and maintain an open conformation and to confer developmentally regulated globin gene expression.
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