Abstract
During immunoglobulin class-switch recombination (CSR), the cytidine deaminase AID induces double-strand breaks into transcribed, repetitive DNA elements called switch sequences. The mechanism that promotes the binding of AID specifically to switch regions remains to be elucidated. Here we used a proteomic screen with in vivo biotinylation of AID to identify the splicing regulator PTBP2 as a protein that interacts with AID. Knockdown of PTBP2 mediated by short hairpin RNA in B cells led to a decrease in binding of AID to transcribed switch regions, which resulted in considerable impairment of CSR. PTBP2 is thus an effector of CSR that promotes the binding of AID to switch-region DNA.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Cell Line, Tumor
-
Cell Proliferation
-
Cytidine Deaminase / genetics
-
Cytidine Deaminase / immunology
-
Cytidine Deaminase / metabolism*
-
DNA / genetics
-
DNA / metabolism*
-
Immunoglobulin Class Switching / genetics
-
Immunoglobulin Switch Region / genetics
-
Mice
-
Mice, Inbred BALB C
-
Mice, Knockout
-
Nerve Tissue Proteins / genetics
-
Nerve Tissue Proteins / immunology
-
Nerve Tissue Proteins / metabolism*
-
Polypyrimidine Tract-Binding Protein / genetics
-
Polypyrimidine Tract-Binding Protein / immunology
-
Polypyrimidine Tract-Binding Protein / metabolism*
-
Protein Binding / genetics
-
RNA, Small Interfering / genetics
-
Transcriptional Activation / genetics
-
Transcriptional Activation / immunology
-
Transgenes / genetics
Substances
-
Nerve Tissue Proteins
-
Ptbp2 protein, mouse
-
RNA, Small Interfering
-
Polypyrimidine Tract-Binding Protein
-
DNA
-
AICDA (activation-induced cytidine deaminase)
-
Cytidine Deaminase