LET-418/Mi2 and SPR-5/LSD1 cooperatively prevent somatic reprogramming of C. elegans germline stem cells.

Throughout their journey to forming new individuals, germline stem cells must remain totipotent, particularly by maintaining a specific chromatin structure. However, the place epigenetic factors occupy in this process remains elusive. So far, "sensitization" of chromatin by modulation of histone arrangement and/or content was believed to facilitate transcription-factor-induced germ cell ...
reprogramming. Here, we demonstrate that the combined reduction of two epigenetic factors suffices to reprogram C. elegans germ cells. The histone H3K4 demethylase SPR-5/LSD1 and the chromatin remodeler LET-418/Mi2 function together in an early process to maintain germ cell status and act as a barrier to block precocious differentiation. This epigenetic barrier is capable of limiting COMPASS-mediated H3K4 methylation, because elevated H3K4me3 levels correlate with germ cell reprogramming in spr-5; let-418 mutants. Interestingly, germ cells deficient for spr-5 and let-418 mainly reprogram as neurons, suggesting that neuronal fate might be the first to be derepressed in early embryogenesis.
Mesh Terms:
Animals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Cell Differentiation, Cell Division, Cell Transformation, Neoplastic, Cellular Reprogramming, Chromatin, DNA-Binding Proteins, Down-Regulation, Female, Gene Expression Regulation, Germ Cells, Histones, Male, Methylation, Mi-2 Nucleosome Remodeling and Deacetylase Complex, Mutation, Neoplasms, Germ Cell and Embryonal, Neurons, Oxidoreductases, N-Demethylating, Protein Binding, Stem Cells
Stem Cell Reports
Date: Apr. 08, 2014
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