Sharma, P.* ; Lioutas, A.* ; Fernandez-Fuentes, N.* ; Quilez, J.* ; Carbonell-Caballero, J.* ; Wright, R.H.G.* ; Di Vona, C.* ; Le Dily, F.* ; Schüller, R. ; Eick, D. ; Oliva, B.* ; Beato, M.*
     
 
    
        
         Arginine citrullination at the C-terminal domain controls RNA polymerase II transcription.
        Arginine citrullination at the C-terminal domain controls RNA polymerase II transcription.
     
    
        
    
    
        
        Mol. Cell 73, 84-96 (2018)
    
    
    
		
		
			
				The post-translational modification of key residues at the C-terminal domain of RNA polymerase II (RNAP2-CTD) coordinates transcription, splicing, and RNA processing by modulating its capacity to act as a landing platform for a variety of protein complexes. Here, we identify a new modification at the CTD, the deimination of arginine and its conversion to citrulline by peptidyl arginine deiminase 2 (PADI2), an enzyme that has been associated with several diseases, including cancer. We show that, among PADI family members, only PADI2 citrullinates R1810 (Cit1810) at repeat 31 of the CTD. Depletion of PADI2 or loss of R1810 results in accumulation of RNAP2 at transcription start sites, reduced gene expression, and inhibition of cell proliferation. Cit1810 is needed for interaction with the P-TEFb (positive transcription elongation factor b) kinase complex and for its recruitment to chromatin. In this way, CTD-Cit1810 favors RNAP2 pause release and efficient transcription in breast cancer cells.
			
			
				
			
		 
		
			
				
					
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        Publikationstyp
        Artikel: Journalartikel
    
 
    
        Dokumenttyp
        Wissenschaftlicher Artikel
    
 
    
        Typ der Hochschulschrift
        
    
 
    
        Herausgeber
        
    
    
        Schlagwörter
        Arginine1810 ; Breast Cancer Cells ; Cell Proliferation ; Citrullination ; P-tefb Complex ; Padi2 ; Proximal Promoter Pausing ; Rna Polymerase Ii Ctd; Multiple Sequence Alignment; Microarray Data; Protein; Expression; Ctd; Genes; Methylation; Elongation; Nucleosome; Reveals
    
 
    
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        Sprache
        englisch
    
 
    
        Veröffentlichungsjahr
        2018
    
 
    
        Prepublished im Jahr 
        
    
 
    
        HGF-Berichtsjahr
        2018
    
 
    
    
        ISSN (print) / ISBN
        1097-2765
    
 
    
        e-ISSN
        1097-4164
    
 
    
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	    Band: 73,  
	    Heft: 1,  
	    Seiten: 84-96 
	    Artikelnummer: ,  
	    Supplement: ,  
	
    
 
  
        
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            Verlag
            Elsevier
        
 
        
            Verlagsort
            50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
        
 
	
        
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        Begutachtungsstatus
        Peer reviewed
    
 
     
    
        POF Topic(s)
        30203 - Molecular Targets and Therapies
    
 
    
        Forschungsfeld(er)
        Helmholtz Diabetes Center
    
 
    
        PSP-Element(e)
        G-502890-001
    
 
    
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        Erfassungsdatum
        2018-12-07