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

Gönczy, P.; Reith, Walter; Barras, Emmanuele; Lisowska-Grospierre, B.; Griscelli, C.; Hadam, M. R.; Mach, Bernard

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Title		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
Authors		Gönczy, P. Reith, Walter Barras, Emmanuele Lisowska-Grospierre, B. Griscelli, C. Hadam, M. R. Mach, Bernard
Published in		Molecular and Cellular Biology. 1989, vol. 9, no. 1, p. 296-302
Abstract		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.
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, Genetic — RNA/analysis
Identifiers		DOI: 10.1128/mcb.9.1.296 PMID: 2467188
Full text		Article - Limited access to UNIGE Other version: http://mcb.asm.org/cgi/reprint/9/1/296.pdf
Structures		Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie
Citation (ISO format)		GÖNCZY, P. et al. 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. In: Molecular and Cellular Biology, 1989, vol. 9, n° 1, p. 296-302. https://archive-ouverte.unige.ch/unige:11276