美国加州大学洛杉矶分校Alexander Hoffmann课题组发现，NF-κB动力学决定巨噬细胞表观基因组重编程的刺激特异性。该研究于2021年6月18日发表于国际一流学术期刊《科学》。

研究人员表示，巨噬细胞的表观基因组可以通过细胞外信号重新编程，但不同刺激实现这一点的程度尚不清楚。核因子κB（NF-κB）是一种转录因子，可被所有病原体相关刺激激活，并可通过激活潜在增强子重新编程表观基因组。

然而，研究人员表明NF-κB仅对一类的刺激做出反应。这种刺激特异性取决于NF-κB活性的时间动态，特别是它是振荡的还是非振荡的。非振荡NF-κB通过持续破坏核小体组蛋白-DNA 相互作用来打开染色质，从而激活调节免疫反应基因表达的潜在增强子。因此，时间动态可以确定转录因子以刺激特异性方式重新编程表观基因组的能力。

附：英文原文

Title: NF-κB dynamics determine the stimulus specificity of epigenomic reprogramming in macrophages

Author: Quen J. Cheng, Sho Ohta, Katherine M. Sheu, Roberto Spreafico, Adewunmi Adelaja, Brooks Taylor, Alexander Hoffmann

Issue&Volume: 2021/06/18

Abstract: The epigenome of macrophages can be reprogrammed by extracellular cues, but the extent to which different stimuli achieve this is unclear. Nuclear factor κB (NF-κB) is a transcription factor that is activated by all pathogen-associated stimuli and can reprogram the epigenome by activating latent enhancers. However, we show that NF-κB does so only in response to a subset of stimuli. This stimulus specificity depends on the temporal dynamics of NF-κB activity, in particular whether it is oscillatory or non-oscillatory. Non-oscillatory NF-κB opens chromatin by sustained disruption of nucleosomal histone–DNA interactions, enabling activation of latent enhancers that modulate expression of immune response genes. Thus, temporal dynamics can determine a transcription factor’s capacity to reprogram the epigenome in a stimulus-specific manner.

DOI: 10.1126/science.abc0269

Source: https://science.sciencemag.org/content/372/6548/1349