The Sm protein methyltransferase PRMT5 is not required for primordial germ cell specification in mice

Ziwei Li; Juehua Yu; Linzi Hosohama; Kevin Nee; Sofia Gkountela; Sonal Chaudhari; Ashley A Cass; Xinshu Xiao; Amander T Clark

doi:10.15252/embj.201489319

The Sm protein methyltransferase PRMT5 is not required for primordial germ cell specification in mice

EMBO J. 2015 Mar 12;34(6):748-58. doi: 10.15252/embj.201489319. Epub 2014 Dec 17.

Authors

Ziwei Li¹, Juehua Yu², Linzi Hosohama³, Kevin Nee¹, Sofia Gkountela¹, Sonal Chaudhari³, Ashley A Cass⁴, Xinshu Xiao⁴, Amander T Clark⁵

Affiliations

¹ 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.
² David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
³ Department of Molecular Cell and Developmental Biology, University of California Los Angeles, Los Angeles, CA, USA.
⁴ 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.
⁵ 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.

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.

Keywords: PGC specification; PRMT5; conditional knockout; germline absence; splicing.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Blotting, Western
Cell Differentiation / physiology*
Computational Biology
DNA Methylation
DNA Primers / genetics
Epigenesis, Genetic / physiology*
Flow Cytometry
Fluorescent Antibody Technique
Gene Expression Regulation, Developmental / physiology*
Gene Knockout Techniques
Genotype
Germ Cells / cytology*
Germ Cells / enzymology
Mice
Positive Regulatory Domain I-Binding Factor 1
Protein Methyltransferases / metabolism*
Protein-Arginine N-Methyltransferases
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Sequence Analysis, RNA
Spliceosomes / metabolism
Transcription Factors / genetics*

Substances

DNA Primers
Prdm1 protein, mouse
Transcription Factors
Positive Regulatory Domain I-Binding Factor 1
Protein Methyltransferases
Prmt5 protein, mouse
Protein-Arginine N-Methyltransferases

Abstract

Publication types

MeSH terms

Substances

Grants and funding