Histone3 lysine4 trimethylation regulated by the facilitates chromatin transcription complex is critical for DNA cleavage in class switch recombination.
Ig class switch recombination (CSR) requires expression of activation-induced cytidine deaminase (AID) and transcription through target switch (S) regions. Here we show that knockdown of the histone chaperone facilitates chromatin transcription (FACT) completely inhibited S region cleavage and CSR in IgA-switch-inducible CH12F3-2A B cells. FACT knockdown did not reduce AID or S region transcripts but did decrease histone3 lysine4 trimethylation (H3K4me3) at both the Sμ and Sα regions. Because knockdown of FACT or H3K4 methyltransferase cofactors inhibited DNA cleavage in H3K4me3-depleted S regions, H3K4me3 may serve as a mark for recruiting CSR recombinase. These findings revealed an unexpected evolutionary conservation between CSR and meiotic recombination.
Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
Andre
A
Stanlie
Masatoshi
M
Aida
Masamichi
M
Muramatsu
Tasuku
T
Honjo
Nasim A
NA
Begum
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D002460:Cell Line; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D019143:Evolution, Molecular; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D017578:Immunoglobulin Class Switching / Q000502:physiology*; D008239:Lysine / Q000235:genetics / Q000378:metabolism; D008540:Meiosis / Q000502:physiology; D008745:Methylation; D051379:Mice; D014158:Transcription, Genetic / Q000502:physiology*; D045567:VDJ Recombinases / Q000235:genetics / Q000378:metabolism; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D002843:Chromatin; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D006657:Histones; C070454:Ssrp1 protein, mouse; D004247:DNA; D045567:VDJ Recombinases; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase; D008239:Lysine