학술논문
PRMT6 activates cyclin D1 expression in conjunction with the transcription factor LEF1.
Document Type
Academic Journal
Author
Schneider L; Goethe University, Institute for Transfusion Medicine and Immunohematology, and German Red Cross Blood Service BaWüHe, Institute Frankfurt, Frankfurt, Germany.; Herkt S; Goethe University, Institute for Transfusion Medicine and Immunohematology, and German Red Cross Blood Service BaWüHe, Institute Frankfurt, Frankfurt, Germany.; Wang L; Department of Eukaryotic Genetics, Institute of Industrial Genetics, University of Stuttgart, Stuttgart, Germany.; Feld C; Department of Eukaryotic Genetics, Institute of Industrial Genetics, University of Stuttgart, Stuttgart, Germany.; Wesely J; Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt am Main, Germany.; Automated Systems and Genomics, The New York Stem Cell Foundation Research Institute, New York, USA.; Kuvardina ON; Goethe University, Institute for Transfusion Medicine and Immunohematology, and German Red Cross Blood Service BaWüHe, Institute Frankfurt, Frankfurt, Germany.; Meyer A; Goethe University, Institute for Transfusion Medicine and Immunohematology, and German Red Cross Blood Service BaWüHe, Institute Frankfurt, Frankfurt, Germany.; Oellerich T; Department of Medicine II, Hematology/Oncology, Goethe University, Frankfurt, Germany.; German Cancer Research Center and German Cancer Consortium, Heidelberg, Germany.; Department of Molecular Diagnostics/Translational Proteomics, Frankfurt Cancer Institute, Frankfurt, Germany.; Häupl B; Department of Medicine II, Hematology/Oncology, Goethe University, Frankfurt, Germany.; German Cancer Research Center and German Cancer Consortium, Heidelberg, Germany.; Department of Molecular Diagnostics/Translational Proteomics, Frankfurt Cancer Institute, Frankfurt, Germany.; Seifried E; Goethe University, Institute for Transfusion Medicine and Immunohematology, and German Red Cross Blood Service BaWüHe, Institute Frankfurt, Frankfurt, Germany.; Bonig H; Goethe University, Institute for Transfusion Medicine and Immunohematology, and German Red Cross Blood Service BaWüHe, Institute Frankfurt, Frankfurt, Germany.; Department of Medicine, Division of Hematology, University of Washington, Seattle, WA, USA.; Lausen J; Department of Eukaryotic Genetics, Institute of Industrial Genetics, University of Stuttgart, Stuttgart, Germany. joern.lausen@iig.uni-stuttgart.de.
Source
Publisher: Nature Pub. Group Country of Publication: United States NLM ID: 101580004 Publication Model: Electronic Cited Medium: Print ISSN: 2157-9024 (Print) Linking ISSN: 21579024 NLM ISO Abbreviation: Oncogenesis Subsets: PubMed not MEDLINE
Subject
Language
English
ISSN
2157-9024
Abstract
The establishment of cell type specific gene expression by transcription factors and their epigenetic cofactors is central for cell fate decisions. Protein arginine methyltransferase 6 (PRMT6) is an epigenetic regulator of gene expression mainly through methylating arginines at histone H3. This way it influences cellular differentiation and proliferation. PRMT6 lacks DNA-binding capability but is recruited by transcription factors to regulate gene expression. However, currently only a limited number of transcription factors have been identified, which facilitate recruitment of PRMT6 to key cell cycle related target genes. Here, we show that LEF1 contributes to the recruitment of PRMT6 to the central cell cycle regulator CCND1 (Cyclin D1). We identified LEF1 as an interaction partner of PRMT6. Knockdown of LEF1 or PRMT6 reduces CCND1 expression. This is in line with our observation that knockdown of PRMT6 increases the number of cells in G1 phase of the cell cycle and decreases proliferation. These results improve the understanding of PRMT6 activity in cell cycle regulation. We expect that these insights will foster the rational development and usage of specific PRMT6 inhibitors for cancer therapy.