title: The Sm protein methyltransferase PRMT5 is not required for primordial germ cell specification in mice.
abstract: 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.
authors.affiliation: 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.
authors.forename: Ziwei
authors.initials: Z
authors.lastname: Li
authors.affiliation: David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Juehua
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Molecular Cell and Developmental Biology, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Linzi
authors.initials: L
authors.lastname: Hosohama
authors.affiliation: 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.
authors.forename: Kevin
authors.initials: K
authors.lastname: Nee
authors.affiliation: 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.
authors.forename: Sofia
authors.initials: S
authors.lastname: Gkountela
authors.affiliation: Department of Molecular Cell and Developmental Biology, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Sonal
authors.initials: S
authors.lastname: Chaudhari
authors.affiliation: Bioinformatics Interdepartmental Program, University of California Los Angeles, Los Angeles, CA, USA Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA, USA Department of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Ashley A
authors.initials: AA
authors.lastname: Cass
authors.affiliation: Bioinformatics Interdepartmental Program, University of California Los Angeles, Los Angeles, CA, USA Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA, USA Department of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Xinshu
authors.initials: X
authors.lastname: Xiao
authors.affiliation: 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 Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA, USA Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA clarka@ucla.edu.
authors.forename: Amander T
authors.initials: AT
authors.lastname: Clark
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology*; D019295:Computational Biology; D019175:DNA Methylation; D017931:DNA Primers / Q000235:genetics; D044127:Epigenesis, Genetic / Q000502:physiology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D055786:Gene Knockout Techniques; D005838:Genotype; D005854:Germ Cells / Q000166:cytology* / Q000201:enzymology; D051379:Mice; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011496:Protein Methyltransferases / Q000378:metabolism*; D011484:Protein-Arginine N-Methyltransferases; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017423:Sequence Analysis, RNA; D017381:Spliceosomes / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D017931:DNA Primers; C513258:Prdm1 protein, mouse; D014157:Transcription Factors; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011496:Protein Methyltransferases; C498518:Prmt5 protein, mouse; D011484:Protein-Arginine N-Methyltransferases
keywords: PGC specification; PRMT5; conditional knockout; germline absence; splicing