Unmethylation of specific sites in the 5' region is critical for the expression of murine alpha Fc gamma R gene.
Three subtypes of murine low-affinity receptors for IgG (Fc gamma RII) have been identified. One is encoded by the alpha Fc gamma R gene, two are encoded by the beta Fc gamma R gene. In the present work, we examined whether DNA methylation might control expression of the alpha Fc gamma R gene. We found that, in DNA from a panel of Fc gamma R(+) and (-) cell lines, two MspI sites of the alpha Fc gamma R gene were selectively unmethylated only in the two cell lines containing alpha transcripts. These sites, separated by a distance of 1.2 kb, are located in the 5' region of the gene. All other MspI sites were methylated in all cell lines. Furthermore, 5-azacytidine induced the demethylation and the expression of the alpha Fc gamma R gene in the Fc gamma R(-) thymoma BW5147. Both alpha Fc gamma R gene transcripts and corresponding protein products became detectable in 5-azacytidine-treated cells. The alpha Fc gamma R gene was also demethylated and expressed in mouse spleen cells cultured with human rIL-2. We conclude that a correlation links the unmethylation and the expression of the alpha Fc gamma R gene in murine cell lines as well as in nontransformed lymphoid cells responding to a physiological stimulus.
Bonnerot
C
C
Laboratoire d'Immunologie Cellulaire et Clinique, INSERM Unité 255, Institut Curie, Paris, France.
Amigorena
S
S
Fridman
W H
WH
Even
J
J
Daëron
M
M
D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics*; D001374:Azacitidine / Q000494:pharmacology; D015152:Blotting, Northern; D015139:Blotting, Southern; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D007376:Interleukin-2 / Q000494:pharmacology; D007962:Leukocytes / Q000502:physiology*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000502:physiology; D008264:Macrophages / Q000502:physiology; D008407:Mast Cells / Q000502:physiology; D008745:Methylation; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D011961:Receptors, Fc / Q000235:genetics*; D017452:Receptors, IgG; D014158:Transcription, Genetic
D000943:Antigens, Differentiation; D007376:Interleukin-2; D012333:RNA, Messenger; D011961:Receptors, Fc; D017452:Receptors, IgG; D001374:Azacitidine