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• W2133064391 abstract "ABSTRACT The human β-globin locus contains five developmentally regulatedβ -type globin genes. All five genes depend on the locus control region (LCR), located at the 5′ end of the locus, for abundant globin gene transcription. The LCR is composed of five DNase I-hypersensitive sites (HSs), at least a subset of which appear to cooperate to form a holocomplex in activating genes within the locus. We previously tested the requirement for proper LCR polarity by inverting it in human β-globin yeast artificial chromosome transgenic mice and observed reduced expression of all theβ -type globin genes regardless of developmental stage. This phenotype clearly demonstrated an orientation-dependent activity of the LCR, although the mechanistic basis for the observed activity was obscure. Here, we describe genetic evidence demonstrating that human HS5 includes enhancer-blocking (insulator) activity that is both CTCF and developmental stage dependent. Curiously, we also observed an attenuating activity in HS5 that was specific to the ε-globin gene at the primitive stage and was independent of the HS5 CTCF binding site. These observations demonstrate that the phenotype observed in the LCR-inverted locus was in part attributable to placing the HS5 insulator between the LCR HS enhancers (HS1 to HS4) and the promoter of the β-globin gene." @default.
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• W2133064391 date "2003-12-01" @default.
• W2133064391 modified "2023-09-23" @default.
• W2133064391 title "Human β-Globin Locus Control Region HS5Contains CTCF- and Developmental Stage-Dependent Enhancer-BlockingActivity in ErythroidCells" @default.
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• W2133064391 doi "https://doi.org/10.1128/mcb.23.24.8946-8952.2003" @default.
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