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Dev Cell. 2017 Oct 23;43(2):227-239.e5. doi: 10.1016/j.devcel.2017.08.021. Epub 2017 Sep 21.

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

Author information

1
Program in Epithelial Biology, Stanford University, 269 Campus Drive, Room 2145, Stanford, CA 94305, USA; Departments of Molecular Biosciences and Dermatology, Northwestern University, 2205 Tech Drive, Hogan 2-100, Evanston, IL 60208, USA. Electronic address: xiaomin.bao@northwestern.edu.
2
Program in Epithelial Biology, Stanford University, 269 Campus Drive, Room 2145, Stanford, CA 94305, USA.
3
Chemical and Systems Biology, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
4
Program in Epithelial Biology, Stanford University, 269 Campus Drive, Room 2145, Stanford, CA 94305, USA; Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304, USA. Electronic address: khavari@stanford.edu.

Abstract

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.

KEYWORDS:

CSNK1a1; GRHL3; PRMT1; chromatin; differentiation; epidermis; interactome; keratinocyte; phosphorylation; progenitors

PMID:
28943242
PMCID:
PMC5659279
[Available on 2018-10-23]
DOI:
10.1016/j.devcel.2017.08.021
[Indexed for MEDLINE]

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