CSNK1a1 Regulates PRMT1 to Maintain the Progenitor State in Self-Renewing Somatic Tissue

Publication date: Available online 21 September 2017
Source:Developmental Cell
Author(s): Xiaomin Bao, Zurab Siprashvili, Brian J. Zarnegar, Rajani M. Shenoy, Eon J. Rios, Natalie Nady, Kun Qu, Angela Mah, Daniel E. Webster, Adam J. Rubin, Glenn G. Wozniak, Shiying Tao, Joanna Wysocka, Paul A. Khavari
Somatic progenitors sustain tissue self-renewal while suppressing premature differentiation. Protein arginine methyltransferases (PRMTs) affect many processes; however, their role in progenitor function is incompletely understood. PRMT1 was found to be the most highly expressed PRMT in epidermal progenitors and the most downregulated PRMT during differentiation. In targeted mouse knockouts and in long-term regenerated human mosaic epidermis in vivo, epidermal PRMT1 loss abolished progenitor self-renewal and led to premature differentiation. Mass spectrometry of the PRMT1 protein interactome identified the CSNK1a1 kinase, which also proved essential for progenitor maintenance. CSNK1a1 directly bound and phosphorylated PRMT1 to control its genomic targeting to PRMT1-sustained proliferation genes as well as PRMT1-suppressed differentiation genes. Among the latter were GRHL3, whose derepression was required for the premature differentiation seen with PRMT1 and CSNK1a1 loss. Maintenance of the progenitors thus requires cooperation by PRMT1 and CSNK1a1 to sustain proliferation gene expression and suppress premature differentiation driven by GRHL3.

Graphical abstract

Teaser

Bao et al. demonstrate an essential role for the arginine methyltransferase PRMT1 in epidermal progenitor maintenance. They further identify the kinase CSNK1a1 as a key PRMT1-interacting protein. CSNK1a1 phosphorylates PRMT1 and cooperates with PRMT1 to suppress GRHL3-mediated terminal differentiation.


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