小鼠树突状细胞响应 LPS 刺激的染色质修饰波,Genome Biology

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小鼠树突状细胞响应 LPS 刺激的染色质修饰波
Genome Biology ( IF 10.1 ) Pub Date : 2018-09-19 , DOI: 10.1186/s13059-018-1524-z
Alexis Vandenbon _{1,

2} , Yutaro Kumagai _{3,

4} , Mengjie Lin ₅ , Yutaka Suzuki ₅ , Kenta Nakai ₆

Affiliation

背景转录因子（TF）和表观遗传修饰在基因表达控制中的重要性已被广泛接受。然而，在细胞外刺激反应过程中 TF 结合、组蛋白修饰和基因表达变化之间的因果关系尚不清楚。在这里，我们分析了树突状细胞响应脂多糖 (LPS) 刺激而在全基因组范围内发生的这些事件的顺序。结果使用 ChIP-seq 时间序列数据集，我们发现 LPS 诱导的不同组蛋白修饰的积累清楚地遵循独特的图案。H3K4me3 的增加似乎与转录激活一致。相比之下，H3K9K14ac 在刺激后早期积累，而 H3K36me3 在稍后时间点积累。与 TF 结合数据的综合分析揭示了 TF 激活与组蛋白修饰动态之间的潜在联系。特别是，LPS 诱导的 H3K9K14ac 和 H3K4me3 增加与 STAT1/2 的结合有关，并且在 Stat1−/− 细胞中严重受损。结论虽然某些组蛋白修饰的短期变化的时间与转录活性的变化一致，但这是其他人则不然。在后一种情况下，修饰的动态更可能反映了刺激诱导的转录因子及其与染色质修饰剂的相互作用的严格调节。

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Waves of chromatin modifications in mouse dendritic cells in response to LPS stimulation

BackgroundThe importance of transcription factors (TFs) and epigenetic modifications in the control of gene expression is widely accepted. However, causal relationships between changes in TF binding, histone modifications, and gene expression during the response to extracellular stimuli are not well understood. Here, we analyze the ordering of these events on a genome-wide scale in dendritic cells in response to lipopolysaccharide (LPS) stimulation.ResultsUsing a ChIP-seq time series dataset, we find that the LPS-induced accumulation of different histone modifications follows clearly distinct patterns. Increases in H3K4me3 appear to coincide with transcriptional activation. In contrast, H3K9K14ac accumulates early after stimulation, and H3K36me3 at later time points. Integrative analysis with TF binding data reveals potential links between TF activation and dynamics in histone modifications. Especially, LPS-induced increases in H3K9K14ac and H3K4me3 are associated with binding by STAT1/2 and were severely impaired in Stat1−/− cells.ConclusionsWhile the timing of short-term changes of some histone modifications coincides with changes in transcriptional activity, this is not the case for others. In the latter case, dynamics in modifications more likely reflect strict regulation by stimulus-induced TFs and their interactions with chromatin modifiers.

更新日期：2018-09-19

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