Histone H2A and H2B are monoubiquitinated at AID-targeted loci.
Histone H2A and H2B are monoubiquitinated at AID-targeted loci.
复制标题
DOI：
10.1371/journal.pone.0011641
复制
发表时间：
2010-07-16
期刊：
影响因子：
3.7
通讯作者：
Larson ED
中科院分区：
文献类型：
--
作者：
Borchert GM;Holton NW;Edwards KA;Vogel LA;Larson ED
体细胞超突变将碱基置换引入重排和表达的免疫球蛋白（Ig）可变区，以促进免疫。该途径需要激活诱导脱氨酶（AID）蛋白启动，该蛋白脱氨胞苷产生尿嘧啶和Ig基因上的UG错配。错配修复和碱基切除修复因子对尿嘧啶的后续处理有助于突变。虽然对某些基因组靶点有选择性，但区分超突变和非超突变位点的染色质修饰尚未定义。在这里，我们发现哺乳动物B细胞中的艾滋病靶向位点含有泛素化的染色质。染色质免疫沉淀（ChIP）分析了组成型超突变Burkitt B细胞系Ramos，发现在两个艾滋病相关位点存在单泛素化形式的组蛋白H2A和H2B，但在表达但未超突变的对照位点不存在。用LPS激活的原代小鼠脾细胞进行类似分析，发现在ChIP上表达的VH和s γ - 3开关区富集了AID和单泛素化H2A和H2B的特异性抗体。在哺乳动物的高突变机制中，AID可能与泛素化的染色质相互作用，因为共聚焦免疫荧光显微镜可以在离散的核灶中看到AID与单泛素化的H2B共定位。我们的研究结果表明，单泛素化组蛋白伴随着活跃的体细胞超突变，揭示了部分组蛋白编码标记艾滋病靶向位点。通过识别与体细胞超突变相关的特定核小体结构，这扩展了目前对超突变期间染色质状态的看法。
Somatic hypermutation introduces base substitutions into the rearranged and expressed immunoglobulin (Ig) variable regions to promote immunity. This pathway requires and is initiated by the Activation Induced Deaminase (AID) protein, which deaminates cytidine to produce uracils and UG mismatches at the Ig genes. Subsequent processing of uracil by mismatch repair and base excision repair factors contributes to mutagenesis. While selective for certain genomic targets, the chromatin modifications which distinguish hypermutating from non-hypermutating loci are not defined. Here, we show that AID-targeted loci in mammalian B cells contain ubiquitinated chromatin. Chromatin immunoprecipitation (ChIP) analysis of a constitutively hypermutating Burkitt's B cell line, Ramos, revealed the presence of monoubiquitinated forms of both histone H2A and H2B at two AID-associated loci, but not at control loci which are expressed but not hypermutated. Similar analysis using LPS activated primary murine splenocytes showed enrichment of the expressed VH and Sγ3 switch regions upon ChIP with antibody specific to AID and to monoubiquitinated H2A and H2B. In the mechanism of mammalian hypermutation, AID may interact with ubiquitinated chromatin because confocal immunofluorescence microscopy visualized AID colocalized with monoubiquitinated H2B within discrete nuclear foci. Our results indicate that monoubiquitinated histones accompany active somatic hypermutation, revealing part of the histone code marking AID-targeted loci. This expands the current view of the chromatin state during hypermutation by identifying a specific nucleosome architecture associated with somatic hypermutation.
登录
查看更多内容
影响因子：
12.3
作者：
Larson ED;Maizels N
通讯作者：
Maizels N
影响因子：
15.3
作者：
Langerak, Petra;Nygren, Anders O. H.;Krijger, Peter H. L.;van den Berk, Paul C. M.;Jacobs, Heinz
通讯作者：
Jacobs, Heinz
影响因子：
64.5
作者：
Revy, P;Muto, T;Durandy, A
通讯作者：
Durandy, A
DOI：
10.1073/pnas.0605146103
发表时间：
2006-08-08
影响因子：
11.1
作者：
Bachl, Juergen;Ertongur, Isin;Jungnickel, Berit
通讯作者：
Jungnickel, Berit
影响因子：
64.8
作者：
Liu, Man;Duke, Jamie L.;Schatz, David G.
通讯作者：
Schatz, David G.