研究人员介绍了"合成调控重组"，这是一个研究基因调控的概念框架，并将其应用于HoxA簇。研究人员合成了变异的大鼠HoxA簇（130至170kb），并将其传递到小鼠基因组的一个异位位置。研究人员发现，一个最小的HoxA簇重现了染色质重塑和转录的正确模式来响应模式化信号，而增加远端增强子则需要充分的转录输出。合成调控重构可以为破译复杂基因组中基因表达的调控逻辑提供一种可推广的策略。
据了解，精确的Hox基因表达对胚胎发育模式至关重要。Hox内转录因子结合和远端增强子元件已成为控制Hox基因表达的主要调控模块。然而，对它们的相对贡献进行量化仍然是难以捉摸的。
附：英文原文
Title: Synthetic regulatory reconstitution reveals principles of mammalian Hox cluster regulation
Author: Sudarshan Pinglay, Milica Bulaji, Dylan P. Rahe, Emily Huang, Ran Brosh, Nicholas E. Mamrak, Benjamin R. King, Sergei German, John A. Cadley, Lila Rieber, Nicole Easo, Timothée Lionnet, Shaun Mahony, Matthew T. Maurano, Liam J. Holt, Esteban O. Mazzoni, Jef D. Boeke
Issue&Volume: 2022-07-01
Abstract: Precise Hox gene expression is crucial for embryonic patterning. Intra-Hox transcription factor binding and distal enhancer elements have emerged as the major regulatory modules controlling Hox gene expression. However, quantifying their relative contributions has remained elusive. Here, we introduce “synthetic regulatory reconstitution,” a conceptual framework for studying gene regulation, and apply it to the HoxA cluster. We synthesized and delivered variant rat HoxA clusters (130 to 170 kilobases) to an ectopic location in the mouse genome. We found that a minimal HoxA cluster recapitulated correct patterns of chromatin remodeling and transcription in response to patterning signals, whereas the addition of distal enhancers was needed for full transcriptional output. Synthetic regulatory reconstitution could provide a generalizable strategy for deciphering the regulatory logic of gene expression in complex genomes.
DOI: abk2820
Source: https://www.science.org/doi/10.1126/science.abk2820