title: Transcription factors that convert adult cell identity are differentially polycomb repressed.
abstract: Transcription factors that can convert adult cells of one type to another are usually discovered empirically by testing factors with a known developmental role in the target cell. Here we show that standard genomic methods (RNA-seq and ChIP-seq) can help identify these factors, as most are more strongly Polycomb repressed in the source cell and more highly expressed in the target cell. This criterion is an effective genome-wide screen that significantly enriches for factors that can transdifferentiate several mammalian cell types including neural stem cells, neurons, pancreatic islets, and hepatocytes. These results suggest that barriers between adult cell types, as depicted in Waddington's "epigenetic landscape", consist in part of differentially Polycomb-repressed transcription factors. This genomic model of cell identity helps rationalize a growing number of transdifferentiation protocols and may help facilitate the engineering of cell identity for regenerative medicine.
authors: Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia United States of America. davisf@janelia.hhmi.org
authors: Fred P
authors: FP
authors: Davis
authors: Sean R
authors: SR
authors: Eddy
mesh_terms: D000818:Animals; D054338:Cell Transdifferentiation; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D015894:Genome, Human; D006657:Histones / Q000502:physiology; D006801:Humans; D051379:Mice; D010641:Phenotype; D063146:Polycomb-Group Proteins / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D006657:Histones; D063146:Polycomb-Group Proteins; D014157:Transcription Factors
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