PADI4 acts as a coactivator of Tal1 by counteracting repressive histone arginine methylation

• Published in: Nature communications Vol. 5; no. 1; p. 3995
• Main Authors: Kolodziej, Stephan, Kuvardina, Olga N, Oellerich, Thomas, Herglotz, Julia, Backert, Ingo, Kohrs, Nicole, Buscató, Estel la, Wittmann, Sandra K, Salinas-Riester, Gabriela, Bonig, Halvard, Karas, Michael, Serve, Hubert, Proschak, Ewgenij, Lausen, Jörn
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 29.05.2014; Nature Pub. Group
• Subjects: Arginine - metabolism; Basic Helix-Loop-Helix Transcription Factors - genetics; Basic Helix-Loop-Helix Transcription Factors - metabolism; CCCTC-Binding Factor; Cell Differentiation - genetics; Cell Line, Tumor; Cytokine Receptor gp130 - genetics; Cytokine Receptor gp130 - metabolism; Epigenesis, Genetic; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; Hematopoiesis - genetics; Hematopoietic Stem Cells; Histones - metabolism; Humans; Hydrolases - genetics; Hydrolases - metabolism; Methylation; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Promoter Regions, Genetic; Protein-Arginine Deiminases; Protein-Arginine N-Methyltransferases - genetics; Protein-Arginine N-Methyltransferases - metabolism; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Repressor Proteins - genetics; Repressor Proteins - metabolism; T-Cell Acute Lymphocytic Leukemia Protein 1
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms4995

The transcription factor Tal1 is a critical activator or repressor of gene expression in hematopoiesis and leukaemia. The mechanism by which Tal1 differentially influences transcription of distinct genes is not fully understood. Here we show that Tal1 interacts with the peptidylarginine deiminase IV (PADI4). We demonstrate that PADI4 can act as an epigenetic coactivator through influencing H3R2me2a. At the Tal1/PADI4 target gene IL6ST the repressive H3R2me2a mark triggered by PRMT6 is counteracted by PADI4, which augments the active H3K4me3 mark and thus increases IL6ST expression. In contrast, at the CTCF promoter PADI4 acts as a repressor. We propose that the influence of PADI4 on IL6ST transcription plays a role in the control of IL6ST expression during lineage differentiation of hematopoietic stem/progenitor cells. These results open the possibility to pharmacologically influence Tal1 in leukaemia.