H3 trimethyl K9 and H3 acetyl K9 chromatin modifications are associated with class switch recombination
H3 trimethyl K9 and H3 acetyl K9 chromatin modifications are associated with class switch recombination
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DOI：
10.1073/pnas.0901368106
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发表时间：
2009-03-31
影响因子：
11.1
通讯作者：
Scharff, Matthew D.
中科院分区：
文献类型：
--
作者：
Kuang, Fei Li;Luo, Zhonghui;Scharff, Matthew D.
类别转换重组（CSR）涉及IG重链（IgH）基因中的DNA重排，其允许相同的可变（V）区与下游恒定区（C）基因中的任一个一起表达，以编码具有许多不同效应子功能的抗体。关于CSR如何靶向不同的C区基因的一个假设是组蛋白修饰增加了特定供体和受体转换区的可接近性和/或募集活化诱导的胞嘧啶脱氨酶（AID）及其相关过程。在这项工作中，我们确定了H3乙酰K9和H3三甲基K9作为组蛋白修饰，与供体和受体开关区域的重组对相关。H3三甲基K9的出现令人惊讶，因为通常认为它标记沉默基因和异染色质。然而，这些组蛋白修饰出现的时间过程，它们与IgH中的区域相关，以及它们的外观独立于AID损伤，表明这两种修饰在靶向CSR中发挥作用。
Class switch recombination (CSR) involves a DNA rearrangement in the Ig heavy chain (IgH) gene that allows the same variable (V) region to be expressed with any one of the downstream constant region (C) genes to encode antibodies with many different effector functions. One hypothesis for how CSR is targeted to different C region genes is that histone modifications increase accessibility and/or recruit activation-induced cytosine deaminase (AID) and its associated processes to particular donor and recipient switch regions. In this work, we identified H3 acetyl K9 and H3 trimethyl K9 as histone modifications that correlate with the recombining pair of donor and recipient switch regions. The appearance of H3 trimethyl K9 is surprising because usually it is thought to mark silent genes and heterochromatin. Nevertheless, the time course of appearance of these histone modifications, the regions in IgH they associate with, and their appearance independent of AID damage suggest that both modifications play a role in targeting CSR.