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For example, in the nematode C. elegans, the ectopic expression of a neuronal identity-inducing transcription factor, CHE-1, can effectively induce CHE-1 target genes in immature cells but not in fully mature non-neuronal cells. To understand the molecular basis of this progressive restriction of cellular plasticity, we screened for C. elegans mutants in which ectopically expressed CHE-1 is able to induce neuronal effector genes in epidermal cells. We identified a ubiquitin hydrolase, usp-48, that restricts cellular plasticity with a notable cellular specificity. Even though we find usp-48 to be very broadly expressed in all tissue types, usp-48 null mutants specifically make epidermal cells susceptible to CHE-1-mediated activation of neuronal target genes. We screened for additional genes that allow epidermal cells to be at least partially reprogrammed by ectopic che-1 expression and identified many additional proteins that restrict cellular plasticity of epidermal cells, including a chromatin-related factor (H3K79 methyltransferase, DOT-1.1), a transcription factor (nuclear hormone receptor NHR-48), two MAPK-type protein kinases (SEK-1 and PMK-1), a nuclear localized O-GlcNAc transferase (OGT-1) and a member of large family of nuclear proteins related to the Rb-associated LIN-8 chromatin factor. These findings provide novel insights into the control of cellular plasticity.<\/jats:p>","DOI":"10.1534\/g3.119.400328","type":"journal-article","created":{"date-parts":[[2019,5,15]],"date-time":"2019-05-15T01:55:59Z","timestamp":1557885359000},"page":"2287-2302","source":"Crossref","is-referenced-by-count":31,"title":["Restriction of Cellular Plasticity of Differentiated Cells Mediated by Chromatin Modifiers, Transcription Factors and Protein Kinases"],"prefix":"10.1093","volume":"9","author":[{"given":"Dylan P","family":"Rahe","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Howard Hughes Medical Institute, Columbia University, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Hobert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,7,1]]},"reference":[{"key":"2021042014035925300_bib1","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1006\/mcbr.2001.0300","article-title":"Isolation and characterization of pmk-(1\u20133): three p38 homologs in Caenorhabditis elegans.","volume":"4","author":"Berman","year":"2001","journal-title":"Mol. 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