Klf4 glutamylation is required for cell reprogramming and early embryonic development in mice.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29593216.
- Also identified by DOI 10.1038/s41467-018-03008-2 and PMC identifier 5871780.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Temporal and spatial-specific regulation of pluripotency networks is largely dependent on the precise modifications of core transcription factors. Misregulation of glutamylation is implicated in severe physiological abnormalities. However, how glutamylation regulates cell reprogramming and pluripotency networks remains elusive. Here we show that cytosolic carboxypeptidases 1 (CCP1) or CCP6 deficiency substantially promotes induced pluripotent cell (iPSC) induction and pluripotency of embryonic stem cells (ESCs). Klf4 polyglutamylation at Glu381 by tubulin tyrosine ligase-like 4 (TTLL4) and TTLL1 during cell reprogramming impedes its lysine 48-linked ubiquitination and sustains Klf4 stability. Klf4-E381A knockin mice display impaired blastocyst development and embryonic lethality. Deletion of TTLL4 or TTLL1 abrogates cell reprogramming and early embryogenesis. Thus, Klf4 polyglutamylation plays a critical role in the regulation of cell reprogramming and pluripotency maintenance.
Medical subject headings
- Cellular Reprogramming
- Gene Expression Regulation, Developmental
- Glutamine
- Induced Pluripotent Stem Cells
- Kruppel-Like Transcription Factors
- Peptide Synthases