UNIGE document Scientific Article
previous document  unige:11276  next document
add to browser collection

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.
Lisowska-Grospierre, B.
Griscelli, C.
Hadam, M. R.
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/metabolismBlotting, SouthernCell Line, TransformedChromatin/ analysisDNA-Binding Proteins/ geneticsDeoxyribonuclease I/diagnostic useGenes, MHC Class IIHLA-D Antigens/ geneticsHerpesvirus 4, Human/metabolismHistocompatibility Antigens Class II/ geneticsHumansImmunologic Deficiency Syndromes/ geneticsMutationPromoter Regions, GeneticRNA/analysis
Stable URL http://archive-ouverte.unige.ch/unige:11276
Full text
Article - document accessible for UNIGE members only Limited access to UNIGE
Other version: http://mcb.asm.org/cgi/reprint/9/1/296.pdf
PMID: 2467188
142 hits and 0 download since 2010-08-27
Export document
Format :
Citation style :