Human recombinant Fab fragments with sub-nanomolar affinities for acetylated histones.
Acetylation of lysines at different sites in the N-terminus of core histones is a common mode of chromatin modification; different combinations of such modifications are associated with distinct patterns of gene expression, replication and repair. Antibodies are usually used to identify and localize particular histone modifications and to correlate their presence with transcription or other cellular processes. This requires antibodies of sufficient specificity and affinity for each of the many modifications that have now been observed. In most instances, polyclonal antibodies have been used but monoclonal antibodies can also be effective. Here we report that a phage-displayed repertoire of rearranged antibody genes from splenic B cells from a patient with systemic lupus contain Fab fragments that can bind native acetylated lysine 8 histone H4. This finding represents the first selection of human antibodies specific for acetylated histone and suggests that lupus antibodies may contribute to dissection of the histone code.
Batova
Iglika
I
Institute of Biology and Immunology, Bulgarian Academy of Sciences, Sofia, Bulgaria.
Kowal
Czeslawa
C
May
Rena
R
Scharff
Matthew D
MD
Diamond
Betty
B
D000107:Acetylation; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000378:metabolism*; D000915:Antibody Affinity; D000918:Antibody Specificity; D001323:Autoantibodies / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D015723:Gene Library; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006657:Histones / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000235:genetics / Q000378:metabolism*; D007135:Immunoglobulin Variable Region / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000378:metabolism
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D006657:Histones; D007140:Immunoglobulin Fab Fragments; D007135:Immunoglobulin Variable Region; D011994:Recombinant Proteins; D051548:Histone Acetyltransferases