Chromatin configuration of the human CD2 gene locus during T-cell development.
To investigate the molecular basis for the tissue-specific expression of the human CD2 gene, its chromatin configuration was assessed by determining DNase I hypersensitivity and the degree of methylation during T-cell lineage commitment and development. Tissue-specific DNase I-hypersensitive sites were found within the 5' promoter region and a region 3' of the gene essential for gene expression. DNase I hypersensitivity of the 5' region correlated strictly with transcriptional activity, whereas hypersensitivity of the 3' region correlated with T-cell progenitor activity or lineage commitment but not necessarily with transcription. Hha I and Hpa II sites around the 5' and 3' regions were undermethylated in CD2-expressing T cells but were more extensively methylated in other cell types. These results define likely regulatory elements both upstream and downstream of the CD2 gene that control its tissue-specific expression. Further, they show that the 3' regulatory region adopts an open chromatin configuration prior to lineage commitment and during early stages of T-cell development before the CD2 gene is transcribed.
Wotton
D
D
Imperial Cancer Research Fund, St. Bartholomew's Hospital, London, United Kingdom.
Flanagan
B F
BF
Owen
M J
MJ
D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics*; D000954:Antigens, Surface / Q000235:genetics*; D015139:Blotting, Southern; D018801:CD2 Antigens; D002460:Cell Line; D002843:Chromatin / Q000648:ultrastructure*; D003850:Deoxyribonuclease I; D005796:Genes; D005802:Genes, MHC Class II; D006801:Humans; D008745:Methylation; D011971:Receptors, Immunologic / Q000235:genetics*; D015183:Restriction Mapping; D013601:T-Lymphocytes / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D018801:CD2 Antigens; D002843:Chromatin; D011971:Receptors, Immunologic; D003850:Deoxyribonuclease I