DNA methylation profiling in human B cells reveals immune regulatory elements and epigenetic plasticity at Alu elements during B-cell activation.
DNA methylation profiling in human B cells reveals immune regulatory elements and epigenetic plasticity at Alu elements during B-cell activation.
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DOI：
10.1101/gr.155473.113
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发表时间：
2013-12
期刊：
影响因子：
7
通讯作者：
Wade PA
中科院分区：
文献类型：
--
作者：
Lai AY;Mav D;Shah R;Grimm SA;Phadke D;Hatzi K;Melnick A;Geigerman C;Sobol SE;Jaye DL;Wade PA
记忆是获得性免疫的一个标志，其中淋巴细胞对以前遇到的抗原产生更好的反应。据推测，记忆淋巴细胞的表观遗传变化有助于它们与幼稚的淋巴细胞在功能上的区别。然而，记忆隔间的表观遗传改变的性质和程度仍然缺乏特征。在这里，我们描述了DNA甲基组和B淋巴细胞亚群的转录组，它们代表了体内暴露抗原前后体液免疫反应的不同阶段。在激活诱导的DNA甲基化缺失中，有很大比例映射到转录因子结合部位。另外一类去甲基化的基因座定位于整个基因组中的Alu元件，并伴随着DNA甲基转移酶3A的抑制。依赖于激活的DNA甲基化变化主要保留在激活的B细胞的后代中，在下游具有不同转录程序的记忆B细胞和浆细胞中产生类似的表观遗传学特征。这些发现提供了对免疫反应中细胞分化过程中基因组甲基化动态的洞察。
Memory is a hallmark of adaptive immunity, wherein lymphocytes mount a superior response to a previously encountered antigen. It has been speculated that epigenetic alterations in memory lymphocytes contribute to their functional distinction from their naive counterparts. However, the nature and extent of epigenetic alterations in memory compartments remain poorly characterized. Here we profile the DNA methylome and the transcriptome of B-lymphocyte subsets representing stages of the humoral immune response before and after antigen exposure in vivo from multiple humans. A significant percentage of activation-induced losses of DNA methylation mapped to transcription factor binding sites. An additional class of demethylated loci mapped to Alu elements across the genome and accompanied repression of DNA methyltransferase 3A. The activation-dependent DNA methylation changes were largely retained in the progeny of activated B cells, generating a similar epigenetic signature in downstream memory B cells and plasma cells with distinct transcriptional programs. These findings provide insights into the methylation dynamics of the genome during cellular differentiation in an immune response.
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影响因子：
64.5
作者：
Fujita, N;Jaye, DL;Wade, PA
通讯作者：
Wade, PA
DOI：
10.1073/pnas.0703872104
发表时间：
2007-08-14
影响因子：
11.1
作者：
Good, Kim L.;Tangye, Stuart G.
通讯作者：
Tangye, Stuart G.
DOI：
10.1084/jem.20100204
发表时间：
2010-08-30
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lai AY;Fatemi M;Dhasarathy A;Malone C;Sobol SE;Geigerman C;Jaye DL;Mav D;Shah R;Li L;Wade PA
通讯作者：
Wade PA
影响因子：
4.4
作者：
Kersh, Ellen N.;Fitzpatrick, David R.;Ahmed, Rafi
通讯作者：
Ahmed, Rafi
影响因子：
30.8
作者：
Broeske, Ann-Marie;Vockentanz, Lena;Rosenbauer, Frank
通讯作者：
Rosenbauer, Frank