Histone3 lysine4 trimethylation regulated by the facilitates chromatin transcription complex is critical for DNA cleavage in class switch recombination
Histone3 lysine4 trimethylation regulated by the facilitates chromatin transcription complex is critical for DNA cleavage in class switch recombination
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DOI：
10.1073/pnas.1016923108
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发表时间：
2010-12-21
影响因子：
11.1
通讯作者：
Begum, Nasim A.
中科院分区：
文献类型：
--
作者：
Stanlie, Andre;Aida, Masatoshi;Begum, Nasim A.
免疫球蛋白类开关重组(CSR)需要表达激活诱导的胞苷脱氨酶(AID)和通过靶开关转录(S)区域。在此，我们证明了组蛋白伴侣蛋白的敲除促进染色质转录(FACT)，完全抑制了IgA开关诱导的CH12F3-2AB细胞中S区域的切割和CSR。事实敲除并没有减少艾滋病或S地区的转录，但确实减少了S亩和S阿尔法区的组蛋白3裂解酶4三甲基化(H3K4me3)。由于FACT或H3K4甲基转移酶辅助因子的敲除抑制了缺失H3K4me3的S区域的DNA切割，H3K4me3可作为招募CSR重组酶的标志。这些发现揭示了CSR和减数分裂重组之间出人意料的进化保守。
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 S mu and S alpha 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.