Remethylation at sites 5' of the murine Lyt-2 gene in association with shutdown of Lyt-2 expression.
We have used hybridomas made by fusing the Lyt-2- AKR thymoma, BW5147, to Lyt-2+ SJL/J lymph node cells to study the regulation of Lyt-2 expression. Fusions of this type yielded hybridomas, the majority of which failed to express Lyt-2. In the minority of hybridomas that did express surface Lyt-2, expression was transient and greatly diminished in terms of molecules of Lyt-2 per cell. Lack of Lyt-2 expression was not due to loss of the gene encoding this cell surface molecule; rather, negative regulation of Lyt-2 appeared to be at the level of transcription (i.e., no Lyt-2 transcripts were detected in these hybridomas). We have shown that the Lyt-2 gene is undermethylated in normal Lyt-2+ T cells, whereas the gene is heavily methylated in Lyt-2- liver cells and in BW5147. Loss of Lyt-2 expression in (BW5147 x Lyt-2+ SJL/J lymph node cell) hybridomas was associated with remethylation of DNA within the Lyt-2 gene and at sites 5' of the Lyt-2 gene.
Carbone
A M
AM
Howard Hughes Medical Institute, Department of Medicine, Denver, CO 80206.
Marrack
P
P
Kappler
J W
JW
D000818:Animals; D000950:Antigens, Ly / Q000235:genetics* / Q000302:isolation & purification; D001483:Base Sequence; D002460:Cell Line; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism*; D005786:Gene Expression Regulation; D006825:Hybridomas / Q000378:metabolism; D008198:Lymph Nodes / Q000473:pathology; D051379:Mice; D008806:Mice, Inbred AKR; D008815:Mice, Inbred Strains; D013601:T-Lymphocytes / Q000378:metabolism*; D013945:Thymoma / Q000235:genetics; D014158:Transcription, Genetic
D000950:Antigens, Ly; D004248:DNA (Cytosine-5-)-Methyltransferases