RRC ID 45909
Author Zuryn S, Ahier A, Portoso M, White ER, Morin MC, Margueron R, Jarriault S.
Title Transdifferentiation. Sequential histone-modifying activities determine the robustness of transdifferentiation.
Journal Science
Abstract Natural interconversions between distinct somatic cell types have been reported in species as diverse as jellyfish and mice. The efficiency and reproducibility of some reprogramming events represent unexploited avenues in which to probe mechanisms that ensure robust cell conversion. We report that a conserved H3K27me3/me2 demethylase, JMJD-3.1, and the H3K4 methyltransferase Set1 complex cooperate to ensure invariant transdifferentiation (Td) of postmitotic Caenorhabditis elegans hindgut cells into motor neurons. At single-cell resolution, robust conversion requires stepwise histone-modifying activities, functionally partitioned into discrete phases of Td through nuclear degradation of JMJD-3.1 and phase-specific interactions with transcription factors that have conserved roles in cell plasticity and terminal fate selection. Our results draw parallels between epigenetic mechanisms underlying robust Td in nature and efficient cell reprogramming in vitro.
Volume 345(6198)
Pages 826-9
Published 2014-8-15
DOI 10.1126/science.1255885
PII 345/6198/826
PMID 25124442
MeSH Amino Acid Sequence Animals Animals, Genetically Modified Caenorhabditis elegans / cytology* Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins / chemistry Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Dedifferentiation Cell Nucleus / metabolism Cell Nucleus / ultrastructure Cell Transdifferentiation* Digestive System / cytology Histone Demethylases / chemistry Histone Demethylases / genetics Histone Demethylases / metabolism* Histone-Lysine N-Methyltransferase / genetics Histone-Lysine N-Methyltransferase / metabolism* Histones / metabolism* Lysine / metabolism Methylation Models, Biological Molecular Sequence Data Motor Neurons / cytology* Transcription Factors / metabolism
IF 41.058
Times Cited 22
C.elegans tm1905