Zhang Chen, Zuo Qisheng, Gao Xiaomin, Hu Cai, Zhou Shujian, Chen Chen, Zou Yichen, Zhao Juanjuan, Zhang Yani, Li Bichun
Joint International Research Laboratory of Agriculture and Agri-Product Safety of Ministry of Education of China, Key Laboratory of Animal Breeding Reproduction and Molecular Design for Jiangsu Province, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China.
College of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang 212000, China.
Animals (Basel). 2021 May 27;11(6):1572. doi: 10.3390/ani11061572.
Primordial germ cells are the ancestors of female and male cells. Current research has shown that long non-coding RNA (lncRNA) and Histone methylation are the pivotal epigenetic factors in the PGC formation. However, there are few studies on the regulatory mechanism of lncRNA in the formation of PGC. Here, we define the lncRNA highly expressed in chicken PGC, lncCPSET1 (chicken-PGC-specifically-expressed transcript 1) This study found that compared with the interference of lncCPSET1/histone methylase Mll2 alone, the PGC formation was severely inhibited with the interference of lncCPSET1 and histone methylase Mll2 jointly in vivo and in vitro. Studies on the transcription level of lncCPSET1 found that H3K4me2 and transcription factor Jun have a positive effect on the activation of lncCPSET1; while DNA hypomethylation inhibits the expression of lncCPSET1. In terms of mechanism, compared with DNA methylation, H3K4me2 dominates lncCPSET1 activation. H3K4me2 can be enriched in the lncCPSET1 promoter, change its chromosome conformation, recruit the transcription factor Jun, and activate the expression of lncCPSET1. Taken together, we confirmed the model that H3K4me2 rather than DNA hypomethylation mediates Jun to regulate lncCPSET1 transcription, which broadens the study of lncCPSET1 pre-transcriptional mechanism.
原始生殖细胞是雌性和雄性细胞的祖先。目前的研究表明，长链非编码RNA（lncRNA）和组蛋白甲基化是原始生殖细胞形成过程中的关键表观遗传因素。然而，关于lncRNA在原始生殖细胞形成过程中的调控机制的研究较少。在此，我们鉴定了在鸡原始生殖细胞中高表达的lncRNA，即lncCPSET1（鸡原始生殖细胞特异性表达转录本1）。本研究发现，与单独干扰lncCPSET1/组蛋白甲基转移酶Mll2相比，在体内和体外联合干扰lncCPSET1和组蛋白甲基转移酶Mll2时，原始生殖细胞的形成受到严重抑制。对lncCPSET1转录水平的研究发现，H3K4me2和转录因子Jun对lncCPSET1的激活有正向作用；而DNA低甲基化则抑制lncCPSET1的表达。在机制方面，与DNA甲基化相比，H3K4me2在lncCPSET1激活中起主导作用。H3K4me2可富集于lncCPSET1启动子，改变其染色体构象，招募转录因子Jun，并激活lncCPSET1的表达。综上所述，我们证实了H3K4me2而非DNA低甲基化介导Jun调控lncCPSET1转录的模型，这拓宽了对lncCPSET1转录前机制的研究。
