The DNA-binding defect observed in major histocompatibility complex class II regulatory mutants concerns only one member of a family of complexes binding to the X boxes of class II promoters.
The X box of major histocompatibility complex class II promoters is essential for proper expression of class II genes. Here we show that two distinct protein-DNA complexes (A and B), which exhibit similar binding characteristics and identical contact points on the X box, can be formed. This suggests the existence of a family of related X box-binding factors. Complex B (and not complex A) is specifically affected in primary combined immunodeficiency, a congenital defect in class II gene regulation. RFX1, the first X box-binding protein cloned, encodes a functionally relevant factor present in complex A and not in complex B as originally suspected. This report also illustrates the need for caution in correlating specific cloned proteins with nuclear factors identified by DNA-binding assays, particularly when dealing with families of related proteins.
Herrero Sanchez
C
C
Department of Genetics and Microbiology, University of Geneva Medical School, Switzerland.
Reith
W
W
Silacci
P
P
Mach
B
B
D001483:Base Sequence; D002461:Cell Line, Transformed; D003001:Cloning, Molecular; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D005802:Genes, MHC Class II; D006801:Humans; D015448:Leukemia, B-Cell / Q000235:genetics / Q000276:immunology; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic; D000071701:Regulatory Factor X Transcription Factors; D000071716:Regulatory Factor X1; D016511:Severe Combined Immunodeficiency / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C000605537:RFX1 protein, human; D000071701:Regulatory Factor X Transcription Factors; D000071716:Regulatory Factor X1; D014157:Transcription Factors; D004247:DNA