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Variegated expression of CD8a resulting from in situ deletion of regulatory sequences

Garefalaki, A., Coles, M., Hirschberg, S., Mavria, G., Norton, T., Hostert, A. and Kioussis, D. (2002) Variegated expression of CD8a resulting from in situ deletion of regulatory sequences. Immunity, 16 (5). pp. 635-647. ISSN 1074-7613

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The developmental and subset-specific expression of the CD8 genes is under the control of a complex array of regulatory elements distributed along the locus and characterized by DNaseI hypersensitivity. Here we describe the phenotype of mice in which hypersensitive sites 1 and 2 (HSS1 and 2) of DNaseI hypersensitive Cluster II (CII), which are located upstream of the CD8 gene, were deleted by targeted homologous recombination of the endogenous locus. Knockout mice exhibit a variegated expression of the CD8 gene, particularly among the immature CD4+8+ TCRlo thymocyte population. We propose that HSS Cluster II regulatory elements are essential in ensuring initiation of chromatin remodeling and establishment of an open configuration in all developing thymocytes that undergo the double-negative to double-positive transition. Furthermore, these sequences contribute to the levels of expression of the CD8 gene.

Item Type: Article
Institution: The University of York
Academic Units: The University of York > Hull York Medical School (York)
Depositing User: York RAE Import
Date Deposited: 30 Jun 2009 15:47
Last Modified: 30 Jun 2009 15:47
Published Version: http://dx.doi.org/10.1016/S1074-7613(02)00308-4
Status: Published
Publisher: Elsevier (Cell Press)
Identification Number: 10.1016/S1074-7613(02)00308-4
URI: http://eprints.whiterose.ac.uk/id/eprint/6294

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