State Key Laboratory of Microbial Technology, Institute of Microbial Technology, Shandong Universitygrid.27255.37, Qingdao, People's Republic of China.
mSystems. 2022 Apr 26;7(2):e0105621. doi: 10.1128/msystems.01056-21. Epub 2022 Mar 30.
Differential transcription of functionally divergent duplicate genes is critical for bacterial cells to properly and competitively function in the environment, but the transcriptional regulation mechanisms remain in mystery. Myxococcus xanthus DK1622 possesses two duplicate s with divergent functions. Here, we report that , an orphan gene located upstream of , encodes a response regulator (RR) and is responsible for the differential expression regulation of duplicate s. This RR protein realizes its negative regulatory role via a novel dual-mode functioning manner: binding to the transcription repressor HrcA to enhance its transcriptional inhibition of duplicate s and binding to the 3' end of the sequence to specifically decrease the transcription of the following . Phosphorylation at the conserved 61 aspartic acid is required to trigger the regulatory functions of MXAN_4468. Pull-down experiment and mutation demonstrated that two noncognate CheA proteins, respectively belonging to the Che8 and Che7 chemosensory pathways, are involved in the protein phosphorylation. A transcriptome analysis, as well as the pull-down experiment, suggested that MXAN_4468 plays a global negative regulatory role in M. xanthus. This study elucidates, for the first time, the regulatory mechanism of differential transcription of bacterial duplicate s and suggests a global regulatory role of a dual-functional orphan RR. Multiply copied s require precise regulation of transcriptions for their divergent cellular functions. Here, we reported that an orphan response regulator (RR) tunes the transcriptional discrepancy of the duplicate s in Myxococcus xanthus DK1622 in a dual-functional mode. This RR protein has a conserved phosphorylation site, and the phosphorylation is required for the regulatory functions. Transcriptomic analysis, as well as a pull-down experiment, suggests that the RR plays a global regulatory role in M. xanthus. This study highlights that the dual-functional orphan RR might be involved in conducting the transcriptional symphony to stabilize the complex biological functions in cells.
功能分歧的重复基因的差异转录对于细菌细胞在环境中正常和竞争地发挥功能至关重要，但转录调控机制仍不清楚。粘细菌 M. xanthus DK1622 拥有两个具有不同功能的重复基因。在这里，我们报告说，位于上游的孤儿基因编码一个响应调节蛋白（RR），负责重复基因的差异表达调控。这种 RR 蛋白通过一种新的双重作用方式实现其负调控作用：与转录抑制物 HrcA 结合，增强其对重复基因的转录抑制作用，并与序列的 3'端结合，特异性降低以下基因的转录。保守的 61 位天冬氨酸的磷酸化是触发 MXAN_4468 调节功能的必要条件。下拉实验和突变表明，两种非同源的 CheA 蛋白，分别属于 Che8 和 Che7 化学感受途径，参与了蛋白磷酸化。转录组分析以及下拉实验表明，MXAN_4468 在粘细菌中发挥全局负调控作用。这项研究首次阐明了细菌重复基因差异转录的调控机制，并提出了双功能孤儿 RR 的全局负调控作用。大量复制的基因需要精确调控转录，以实现其细胞功能的差异。在这里，我们报道了一个孤儿响应调节蛋白（RR）以双重功能模式调节粘细菌 M. xanthus DK1622 中重复基因的转录差异。该 RR 蛋白具有一个保守的磷酸化位点，磷酸化是调节功能所必需的。转录组分析以及下拉实验表明，RR 在 M. xanthus 中发挥全局调节作用。这项研究强调，双功能孤儿 RR 可能参与了转录交响乐的演奏，以稳定细胞中复杂的生物学功能。
