Arginine methylation provides epigenetic transcription memory for retinoid-induced differentiation in myeloid cells
Arginine methylation provides epigenetic transcription memory for retinoid-induced differentiation in myeloid cells
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DOI：
10.1128/mcb.25.13.5648-5663.2005
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发表时间：
2005-07-01
影响因子：
5.3
通讯作者：
Nagy, L
中科院分区：
文献类型：
--
作者：
Balint, BL;Szanto, A;Nagy, L
细胞分化受基因表达变化的控制，但同时，细胞的身份需要在成熟过程中通过多次细胞分裂来维持。在骨髓细胞系中，类维生素A诱导基因表达和充分表征的两步谱系特异性分化。为了确定有助于细胞转录记忆的机制，我们分析了组织转谷氨酰胺酶调节区域发生的表观遗传变化，该基因的表达与类维生素A诱导的分化密切相关。在这里，我们报告说，骨髓分化的中间或“启动”状态的诱导与 H4 精氨酸 3 的增加和 H3 赖氨酸 4 甲基化的减少有关。这些修饰发生在转录之前，似乎为染色质随后的激素调节转录做好了准备。此外，甲基转移酶活性的抑制、预乙酰化或 PAW 酶的激活会减弱类视黄醇调节的基因表达，而甲基转移酶 PRMT1 的过度表达则增强类视黄醇的反应性。综上所述，我们的结果表明，H4 精氨酸 3 甲基化是一种真正的正表观遗传标记和转录反应性调节剂以及细胞分化过程中的信号整合机制，因此可能提供表观遗传记忆。
Cellular differentiation is governed by changes in gene expression, but at the same time, a cell's identity needs to be maintained through multiple cell divisions during maturation. In myeloid cell lines, retinoids induce gene expression and a well-characterized two-step lineage-specific differentiation. To identify mechanisms that contribute to cellular transcriptional memory, we analyzed the epigenetic changes taking place on regulatory regions of tissue transglutaminase, a gene whose expression is tightly linked to retinoid-induced differentiation. Here we report that the induction of an intermediary or "primed" state of myeloid differentiation is associated with increased H4 arginine 3 and decreased H3 lysine 4 methylation. These modifications occur before transcription and appear to prime the chromatin for subsequent hormone-regulated transcription. Moreover, inhibition of methyltransferase activity, preacetylation, or activation of the enzyme PAW attenuated retinoid-regulated gene expression, while overexpression of PRMT1, a methyltransferase, enhanced retinoid responsiveness. Taken together, our results suggest that H4 arginine 3 methylation is a bona fide positive epigenetic marker and regulator of transcriptional responsiveness as well as a signal integration mechanism during cell differentiation and, as such, may provide epigenetic memory.