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.
- URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2467188
Keywords: B-Lymphocytes/metabolism ; Blotting ; Southern ; Cell Line ; Transformed ; Chromatin/*analysis ; DNA-Binding Proteins/*genetics ; Deoxyribonuclease I/diagnostic use ; *Genes ; MHC Class II ; HLA-D Antigens/*genetics ; Herpesvirus 4 ; Human/metabolism ; Histocompatibility Antigens Class II/*genetics ; Humans ; Immunologic Deficiency Syndromes/*genetics ; Mutation ; *Promoter Regions (Genetics) ; RNA/analysis ; Research Support ; Non-U.S. Gov't
Department of Microbiology, University of Geneva Medical School, Switzerland.
Record created on 2006-08-24, modified on 2016-08-08