Li Ziwei, Yu Juehua, Hosohama Linzi, Nee Kevin, Gkountela Sofia, Chaudhari Sonal, Cass Ashley A, Xiao Xinshu, Clark Amander T
Department of Molecular Cell and Developmental Biology, University of California Los Angeles, Los Angeles, CA, USA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles, Los Angeles, CA, USA.
David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
EMBO J. 2015 Mar 12;34(6):748-58. doi: 10.15252/embj.201489319. Epub 2014 Dec 17.
PRMT5 is a type II protein arginine methyltransferase with roles in stem cell biology, reprograming, cancer and neurogenesis. During embryogenesis in the mouse, it was hypothesized that PRMT5 functions with the master germline determinant BLIMP1 to promote primordial germ cell (PGC) specification. Using a Blimp1-Cre germline conditional knockout, we discovered that Prmt5 has no major role in murine germline specification, or the first global epigenetic reprograming event involving depletion of cytosine methylation from DNA and histone H3 lysine 9 dimethylation from chromatin. Instead, we discovered that PRMT5 functions at the conclusion of PGC reprograming I to promote proliferation, survival and expression of the gonadal germline program as marked by MVH. We show that PRMT5 regulates gene expression by promoting methylation of the Sm spliceosomal proteins and significantly altering the spliced repertoire of RNAs in mammalian embryonic cells and primordial cells.
PRMT5是一种II型蛋白质精氨酸甲基转移酶，在干细胞生物学、重编程、癌症和神经发生中发挥作用。在小鼠胚胎发生过程中，有人提出PRMT5与主要生殖系决定因子BLIMP1共同发挥作用，以促进原始生殖细胞（PGC）的特化。通过使用Blimp1-Cre生殖系条件性敲除，我们发现Prmt5在小鼠生殖系特化或涉及DNA中胞嘧啶甲基化缺失和染色质中组蛋白H3赖氨酸9二甲基化缺失的首次全基因组表观遗传重编程事件中没有主要作用。相反，我们发现PRMT5在PGC重编程I结束时发挥作用，以促进由MVH标记的性腺生殖系程序的增殖、存活和表达。我们表明，PRMT5通过促进Sm剪接体蛋白的甲基化来调节基因表达，并显著改变哺乳动物胚胎细胞和原始细胞中RNA的剪接谱。
