Gurdon Institute and Department of Pathology, Cambridge, UK.
Cell Rep. 2012 Sep 27;2(3):470-7. doi: 10.1016/j.celrep.2012.08.016. Epub 2012 Sep 20.
The JAK2 tyrosine kinase is a critical mediator of cytokine-induced signaling. It plays a role in the nucleus, where it regulates transcription by phosphorylating histone H3 at tyrosine 41 (H3Y41ph). We used chromatin immunoprecipitation coupled to massively parallel DNA sequencing (ChIP-seq) to define the genome-wide pattern of H3Y41ph in human erythroid leukemia cells. Our results indicate that H3Y41ph is located at three distinct sites: (1) at a subset of active promoters, where it overlaps with H3K4me3, (2) at distal cis-regulatory elements, where it coincides with the binding of STAT5, and (3) throughout the transcribed regions of active, tissue-specific hematopoietic genes. Together, these data extend our understanding of this conserved and essential signaling pathway and provide insight into the mechanisms by which extracellular stimuli may lead to the coordinated regulation of transcription.
JAK2 酪氨酸激酶是细胞因子诱导信号的关键介质。它在核内发挥作用，通过磷酸化组蛋白 H3 的酪氨酸 41（H3Y41ph）来调节转录。我们使用染色质免疫沉淀结合大规模平行 DNA 测序（ChIP-seq）来定义人类红细胞白血病细胞中 H3Y41ph 的全基因组模式。我们的结果表明，H3Y41ph 位于三个不同的位置：（1）在一组活跃的启动子上，与 H3K4me3 重叠；（2）在远端顺式调控元件上，与 STAT5 的结合一致；（3）在活跃的、组织特异性的造血基因的转录区域内。总之，这些数据扩展了我们对这个保守和基本信号通路的理解，并为细胞外刺激如何导致转录的协调调节提供了深入了解。
