Li Yanan, Hu Yueyan, Zhu Zhu, Zhao Kaili, Liu Guodong, Wang Lushan, Qu Yinbo, Zhao Jian, Qin Yuqi
1National Glycoengineering Research Center, Shandong University, Qingdao, 266237 China.
2State Key Lab of Microbial Technology, Shandong University, Qingdao, 266237 China.
Biotechnol Biofuels. 2019 Aug 20;12:198. doi: 10.1186/s13068-019-1539-z. eCollection 2019.
Enzymatic hydrolysis of lignocellulose by fungi is a key step in global carbon cycle and biomass utilization. Cellulolytic enzyme production is tightly controlled at a transcriptional level. Here, we investigated the roles of different histone lysine methylation modifications in regulating cellulolytic enzyme gene expression, as histone lysine methylation is an important process of chromatin regulation associated with gene transcription.
Set1 and Set2 in , orthologs of Set1 and Set2 in budding yeast, were associated with the methylation of histone H3 lysine 4 (H3K4) and lysine 36 (H3K36). Cellulolytic enzyme production was extensively upregulated by the disruption of Set2, but was significantly downregulated by the disruption of Set1. We revealed that the activation of cellulolytic enzyme genes was accompanied by the increase of H3K4me3 signal, as well as the decrease of H3K36me1 and H3K36me3 signal on specific gene loci. The repression of cellulolytic enzyme genes was accompanied by the absence of global H3K4me1 and H3K4me2. An increase in the H3K4me3 signal by disruption was eliminated by the further disruption of and accompanied by the repressed cellulolytic enzyme genes. The active or repressed genes were not always associated with transcription factors.
H3K4 methylation is an active marker of cellulolytic enzyme production, whereas H3K36 methylation is a marker of repression. A crosstalk occurs between H3K36 and H3K4 methylation, and Set2 negatively regulates cellulolytic enzyme production by antagonizing the Set1-H3K4me3 pathway. The balance of H3K4 and H3K36 methylation is required for the normal transcription of cellulolytic enzyme genes. These results extend our previous understanding that cellulolytic enzyme gene transcription is primarily controlled by transcription factors.
真菌对木质纤维素的酶促水解是全球碳循环和生物质利用的关键步骤。纤维素分解酶的产生在转录水平上受到严格控制。在这里,我们研究了不同组蛋白赖氨酸甲基化修饰在调节纤维素分解酶基因表达中的作用,因为组蛋白赖氨酸甲基化是与基因转录相关的染色质调节的重要过程。
里氏木霉中的Set1和Set2,即芽殖酵母中Set1和Set2的直系同源物,与组蛋白H3赖氨酸4(H3K4)和赖氨酸36(H3K36)的甲基化有关。Set2的破坏广泛上调了纤维素分解酶的产生,但Set1的破坏则显著下调了纤维素分解酶的产生。我们发现,纤维素分解酶基因的激活伴随着特定基因位点上H3K4me3信号的增加,以及H3K36me1和H3K36me3信号的减少。纤维素分解酶基因的抑制伴随着全局H3K4me1和H3K4me2的缺失。Set1破坏导致的H3K4me3信号增加被Set2的进一步破坏消除,并伴随着纤维素分解酶基因的抑制。活跃或受抑制的基因并不总是与转录因子相关。
H3K4甲基化是纤维素分解酶产生的活性标记,而H3K36甲基化是抑制标记。H3K36和H3K4甲基化之间存在相互作用,Set2通过拮抗Set1-H3K4me3途径负向调节纤维素分解酶的产生。纤维素分解酶基因的正常转录需要H3K4和H3K36甲基化的平衡。这些结果扩展了我们之前对纤维素分解酶基因转录主要由转录因子控制的理解。