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Identification of a stimulus‐dependent DNase I hypersensitive site between the Iα and Cα exons during immunoglobulin heavy chain class switch recombination
Author(s) -
Ono Santa Jeremy,
Zhou Gang,
Tai Albert K.F.,
Inaba Mayumi,
Kinoshita Kazuo,
Honjo Tasuku
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)01151-0
Subject(s) - recombinase , immunoglobulin class switching , biology , recombination signal sequences , genetics , recombination , chromatin , dna , flp frt recombination , immunoglobulin heavy chain , hypersensitive site , locus (genetics) , microbiology and biotechnology , recombinant dna , site specific recombination , genetic recombination , gene , antibody , recombination activating gene , deoxyribonuclease i , b cell , base sequence
The complete humoral response to foreign antigen depends upon two distinct recombination events within the heavy chain locus of immunoglobulin. The first recombination event takes place in what will become the antigen combining site of the antibody molecule, encoded by V, D and J segments. The second recombination event involves the looping‐out of large spans of DNA which separate the various clusters of heavy chain exons which define the different immunoglobulin isotypes, or classes. While a great deal has been learned about the nature of the VDJ recombinase, very little is known about the nature of the class‐switch recombinase. Using a cell system where class‐switch recombination occurs primarily to the IgA locus, we have looked for stimulus‐dependent changes in the chromatin structure of the IgA locus which might result from interactions between components of the recombinase and cis ‐elements within the region. We present evidence that strongly suggests that the class‐switch recombinase interacts between the Iα and Cα exons of IgA, just upstream of the highly reiterated DR1 and DR2 elements. However, although multiple potential SMAD‐4 sites are located precisely within the DNase I hypersensitive site and 160 bp upstream of that site, we failed to detect any evidence of DNA/protein interactions near the hypersensitive site. Moreover, recombinant SMAD‐3/4 proteins fail to interact with these sites with appreciable affinity in vitro. These data suggest that some other structural alteration at this site (e.g. RNA/DNA hybrid) may mediate the nuclease sensitivity.