title: Epigenetic mechanisms of Groucho/Grg/TLE mediated transcriptional repression.
abstract: The repression of transcription, through the concerted actions of tissue specific DNA binding proteins, Polycomb repressor complexes, and DNA methylation, is essential for maintaining stem cell pluripotency and for cell fate specification in development. In this report, we show that recruitment of the co-repressor protein Grg4 to a Pax DNA-binding site displaces the adaptor protein PTIP and a histone H3K4me complex. Grg4 recruits the arginine methyltransferase PRMT5 to chromatin resulting in symmetric H4R3 dimethylation. PRMT5 is essential for recruiting Polycomb proteins, in a Pax2/Grg4 dependent manner, which results in H3K27 methylation. These data define the early epigenetic events in response to Pax/Grg mediated gene repression and demonstrate that a single DNA binding protein can recruit either an activator or a repressor complex depending on the availability of Grg4. These data suggest a model for understanding the initiation of Groucho/Grg/TLE mediated gene silencing.
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA. sanjeevk@umich.edu
authors.forename: Sanjeevkumar R
authors.initials: SR
authors.lastname: Patel
authors.forename: Samina S
authors.initials: SS
authors.lastname: Bhumbra
authors.forename: Raghavendra S
authors.initials: RS
authors.lastname: Paknikar
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Dressler
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D004268:DNA-Binding Proteins; D044127:Epigenesis, Genetic; D020868:Gene Silencing; D057809:HEK293 Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D008957:Models, Genetic; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D063146:Polycomb-Group Proteins; D011496:Protein Methyltransferases / Q000378:metabolism / Q000502:physiology; D021381:Protein Transport; D011484:Protein-Arginine N-Methyltransferases; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; D009687:Nuclear Proteins; C485876:PAXIP1 protein, human; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins; C465817:TLE4 protein, human; D011496:Protein Methyltransferases; C400529:PRMT5 protein, human; D011484:Protein-Arginine N-Methyltransferases