CSNK1a1 Regulates PRMT1 to Maintain the Progenitor State in Self-Renewing Somatic Tissue
| Autor: | Xiaomin Bao, Natalie Nady, Shiying Tao, Eon J. Rios, Glenn G. Wozniak, Joanna Wysocka, Paul A. Khavari, Angela Mah, Kun Qu, Zurab Siprashvili, Adam J. Rubin, Dan E. Webster, Brian J. Zarnegar, Rajani M Shenoy |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Keratinocytes
0301 basic medicine Protein-Arginine N-Methyltransferases Somatic cell Biology Article General Biochemistry Genetics and Molecular Biology Mice 03 medical and health sciences Gene expression Animals Humans Cell Self Renewal Phosphorylation Progenitor cell Molecular Biology Cells Cultured Gene knockout Progenitor Mice Knockout Epidermis (botany) Stem Cells Infant Newborn Casein Kinase Ialpha Gene targeting Cell Differentiation Cell Biology Cell biology Chromatin 030104 developmental biology Epidermal Cells Epidermis Developmental Biology |
| Zdroj: | Developmental Cell. 43:227-239.e5 |
| ISSN: | 1534-5807 |
| DOI: | 10.1016/j.devcel.2017.08.021 |
| Popis: | Summary 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|