Variegated expression of CD8α resulting from in situ deletion of regulatory sequences

被引：44

作者：

Garefalaki, A ^{[1
]}

Coles, M ^{[1
]}

Hirschberg, S ^{[1
]}

Mavria, G ^{[1
]}

Norton, T ^{[1
]}

Hostert, A ^{[1
]}

Kioussis, D ^{[1
]}

机构：

[1] Natl Inst Med Res, London NW7 1AA, England

来源：

IMMUNITY | 2002年 / 16卷 / 05期

基金：

英国医学研究理事会;

关键词：

D O I：

10.1016/S1074-7613(02)00308-4

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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 DNasel hypersensitivity. Here we describe the phenotype of mice in which hypersensitive sites 1 and 2 (HSS1 and 2) of DNasel hypersensitive Cluster II (CII), which are located upstream of the CD8alpha gene, were deleted by targeted homologous recombination of the endogenous locus. Knockout mice exhibit a variegated expression of the CD8alpha 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 CD8alpha gene.

引用

页码：635 / 647

页数：13

共 35 条

[1] Interaction of the nuclear matrix-associated region (MAR)-binding proteins, SATB1 and CDP/Cux, with a MAR element (L2a) in an upstream regulatory region of the mouse CD8a gene [J].