Regulation of the Th2 Cytokine Locus by a Locus Control Region

3 Department of Molecular Biophysics suppressive effects of flanking DNA sequences (Gros-veld et al., 1987; Milot et al., 1996). The best knownand Biochemistry Yale University example of an LCR is in the human-globin gene cluster. The human -globin locus contains five genes, the ex-New Haven, Connecticut 06520 pression of which is developmentally controlled. The responsible element for this coordinate regulation is the -globin LCR, which is composed of five DNase I hyper-Summary sensitive sites located upstream of the -globin gene, the most 5 gene of the -globin gene cluster. Experi-The Th2 cytokine genes IL4, IL5, and IL13 are clustered mentally, an LCR can be defined as an element that gives and expressed in a cell lineage-specific manner. We transgene copy number-dependent and integration site-investigated the global locus-specific regulation of independent expression to linked genes in transgenic these genes using BAC transgenic mice containing the mice (reviewed in Li et al., 2002; Engel and Tanimoto, murine Th2 cytokine cluster carrying an IL4 promoter- 2000; Festenstein and Kioussis, 2000). luciferase reporter. IL4 promoter activity in effector Coordinated expression of Th2 cytokine genes wa