macroH2AI-dependent silencing of endogenous murine leukemia viruses
macroH2AI-dependent silencing of endogenous murine leukemia viruses
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DOI：
10.1128/mcb.01362-07
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发表时间：
2008-03-01
影响因子：
5.3
通讯作者：
Pehrson, John R.
中科院分区：
文献类型：
--
作者：
Changolkar, Lakshmi N.;Singh, Geetika;Pehrson, John R.
我们发现，macroH 2A 1组蛋白变体是重要的抑制内源性小鼠白血病病毒（MLV）在小鼠肝脏中的表达。完整的MLV前病毒和env缺失的前病毒在正常小鼠肝脏中几乎是沉默的，并且在macroH 2A 1敲除的肝脏中显示出实质性的去抑制。相比之下，在pro-pol的5'端具有缺失的MLV前病毒在正常肝脏中表达，并且在敲除肝脏中显示相对低水平的去阻遏。macroH 2A 1核小体在内源性MLV上富集，最高富集发生在pro-pol的5'端。macroH 2A 1的缺失还导致MLV前病毒5'端DNA甲基化的局部缺失。这些结果表明，macroH 2A 1组蛋白在体内沉默内源性MLV中具有重要作用，并表明特定的内部NILV序列被macroH 2A 1依赖性沉默机制靶向。
We show that macroH2A1 histone variants are important for repressing the expression of endogenous murine leukemia viruses (MLVs) in mouse liver. Intact MLV proviruses and proviruses with deletions in env were nearly silent in normal mouse liver and showed substantial derepression in macroH2A1 knockout liver. In contrast, MLV proviruses with a deletion in the 5' end of pro-pol were expressed in normal liver and showed relatively low levels of derepression in knockout liver. macroH2A1 nucleosomes were enriched on endogenous MLVs, with the highest enrichment occurring on the 5' end of pro-pol. The absence of macroH2A1 also led to a localized loss of DNA methylation on the 5' ends of MLV proviruses. These results demonstrate that macroH2A1 histones have a significant role in silencing endogenous MLVs in vivo and suggest that specific internal NILV sequences are targeted by a macroH2A1-dependent silencing mechanism.