Inherited immunodeficiency with a defect in a major histocompatibility complex class II promoter-binding protein differs in the chromatin structure of the HLA-DRA gene.
A defect in a trans-regulatory factor which controls major histocompatibility complex class II gene expression is responsible for an inherited form of immunodeficiency with a lack of expression of human leukocyte antigen (HLA) class II antigens. We have recently described and cloned an HLA class II promoter DNA-binding protein, RF-X, present in normal B cells and absent in these class II-deficient regulatory mutants. Here we report that these in vitro results correlate with a specific change in the chromatin structure of the class II promoter: two prominent DNase I-hypersensitive sites were identified in the promoter of the HLA-DRA gene in normal B lymphocytes and found to be absent in the class II-deficient mutant cells. The same two prominent DNase I-hypersensitive sites were observed in normal fibroblastic cells induced by gamma interferon to express class II genes. Interestingly, they were also observed in the uninduced class II-negative fibroblastic cells, which have also been shown to have a normal RF-X binding pattern. We conclude that the two DNase I-hypersensitive sites in the HLA-DRA promoter reflect features in chromatin structure which correlate with the binding of the trans-acting factor RF-X and which are necessary but not sufficient for the expression of class II genes.
Gönczy
P
P
Department of Microbiology, University of Geneva Medical School, Switzerland.
Reith
W
W
Barras
E
E
Lisowska-Grospierre
B
B
Griscelli
C
C
Hadam
M R
MR
Mach
B
B
D001402:B-Lymphocytes / Q000378:metabolism; D015139:Blotting, Southern; D002461:Cell Line, Transformed; D002843:Chromatin / Q000032:analysis*; D004268:DNA-Binding Proteins / Q000235:genetics*; D003850:Deoxyribonuclease I; D005802:Genes, MHC Class II; D006681:HLA-D Antigens / Q000235:genetics*; D004854:Herpesvirus 4, Human / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D009154:Mutation; D011401:Promoter Regions, Genetic; D012313:RNA / Q000032:analysis
D002843:Chromatin; D004268:DNA-Binding Proteins; D006681:HLA-D Antigens; D000949:Histocompatibility Antigens Class II; D012313:RNA; D003850:Deoxyribonuclease I