Jin Li Hua, Choi Jung Kyoon, Kim Byungil, Cho Hwan Sung, Kim Jihyun, Kim-Ha Jeongsil, Kim Young-Joon
Department of Biochemistry, Yonsei University, Seoul, Republic of Korea.
Mol Cell Biol. 2009 Mar;29(6):1515-25. doi: 10.1128/MCB.01239-08. Epub 2009 Jan 12.
Drosophila producing a mutant form of the putative transcription coregulator, Split ends (Spen), originally identified in the analysis of neuronal development, display diverse immune defects. In order to understand the role of Spen in the innate immune response, we analyzed the transcriptional defects associated with spen mutant hemocytes and their relationship to the Notch signaling pathways. Spen is regulated by the Notch pathway in the lymph glands and is required for Notch-dependent activation of a large number of genes involved in energy metabolism and differentiation. Analysis of the epigenetic marks associated with Spen-dependent genes indicates that Spen performs its function as a coactivator by regulating chromatin modification. Intriguingly, expression of the Spen-dependent genes was transiently downregulated in a Notch-dependent manner by the Dif activated upon recognition of pathogen-associated molecules, demonstrating the existence of cross talk between hematopoietic regulation and the innate immune response. Our observations reveal a novel connection between the Notch and Toll/IMD signaling pathways and demonstrate a coactivating role for Spen in activating Notch-dependent genes in differentiating cells.
最初在神经元发育分析中被鉴定出的果蝇，产生一种假定的转录共调节因子“分裂末端”（Spen）的突变形式，表现出多种免疫缺陷。为了了解Spen在先天免疫反应中的作用，我们分析了与spen突变血细胞相关的转录缺陷及其与Notch信号通路的关系。Spen在淋巴腺中受Notch通路调控，是Notch依赖性激活大量参与能量代谢和分化的基因所必需的。对与Spen依赖性基因相关的表观遗传标记的分析表明，Spen通过调节染色质修饰发挥其作为共激活因子的功能。有趣的是，在识别病原体相关分子后被激活的Dif以Notch依赖性方式瞬时下调Spen依赖性基因的表达，这表明造血调节与先天免疫反应之间存在相互作用。我们的观察结果揭示了Notch和Toll/IMD信号通路之间的新联系，并证明了Spen在分化细胞中激活Notch依赖性基因方面具有共激活作用。
