This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Balint, B. L. Articles by Nagy, L. Search for Related Content PubMed PubMed Citation Articles by Balint, B. L. Articles by Nagy, L.

Arginine Methylation Provides Epigenetic Transcription Memory for Retinoid-Induced Differentiation in Myeloid Cells

Balint L. Balint,¹ Attila Szanto,¹ Andras Madi,^1,5 Uta-Maria Bauer,² Petra Gabor,¹ Szilvia Benko,^1, Laszlo G. Puskás,³ Peter J. A. Davies,⁴ and Laszlo Nagy^1*

Department of Biochemistry and Molecular Biology, Research Center for Molecular Medicine, University of Debrecen, Medical and Health Science Center,,¹ Signaling and Apoptosis Research Group of the Hungarian Academy of Sciences, Nagyerdei krt. 98, Debrecen H-4012, Hungary,⁵ Institute for Molecular Biology and Tumor Research, Philipps-University Marburg, Emil-Mannkopff-Str. 2, 35033 Marburg, Germany,² Laboratory of Functional Genomics, Biological Research Center of the Hungarian Academy of Sciences, Temesvári krt. 62, Szeged H-6726, Hungary,³ Department of Integrative Biology and Pharmacology, Medical School, University of Texas—Houston, 6431 Fannin, Houston, Texas 77030⁴

Received 16 August 2004/ Returned for modification 15 September 2004/ Accepted 31 March 2005

Cellular differentiation is governed by changes in gene expression, but at the same time, a cell's identity needs to be maintained through multiple cell divisions during maturation. In myeloid cell lines, retinoids induce gene expression and a well-characterized two-step lineage-specific differentiation. To identify mechanisms that contribute to cellular transcriptional memory, we analyzed the epigenetic changes taking place on regulatory regions of tissue transglutaminase, a gene whose expression is tightly linked to retinoid-induced differentiation. Here we report that the induction of an intermediary or "primed" state of myeloid differentiation is associated with increased H4 arginine 3 and decreased H3 lysine 4 methylation. These modifications occur before transcription and appear to prime the chromatin for subsequent hormone-regulated transcription. Moreover, inhibition of methyltransferase activity, preacetylation, or activation of the enzyme PAD4 attenuated retinoid-regulated gene expression, while overexpression of PRMT1, a methyltransferase, enhanced retinoid responsiveness. Taken together, our results suggest that H4 arginine 3 methylation is a bona fide positive epigenetic marker and regulator of transcriptional responsiveness as well as a signal integration mechanism during cell differentiation and, as such, may provide epigenetic memory.

Present address: Department of Immunology, University of Debrecen, Medical and Health Science Center, Nagyerdei krt. 98, Debrecen H-4012, Hungary.

This article has been cited by other articles:

• Kleinschmidt, M. A., Streubel, G., Samans, B., Krause, M., Bauer, U.-M. (2008). The protein arginine methyltransferases CARM1 and PRMT1 cooperate in gene regulation. Nucleic Acids Res 0: gkn166v1-gkn166 [Abstract] [Full Text]  
• Bermejo-Alvarez, P., Rizos, D., Rath, D., Lonergan, P., Gutierrez-Adan, A. (2008). Epigenetic differences between male and female bovine blastocysts produced in vitro. Physiol. Genomics 32: 264-272 [Abstract] [Full Text]  
• Bai, P., Houten, S. M., Huber, A., Schreiber, V., Watanabe, M., Kiss, B., de Murcia, G., Auwerx, J., Murcia, J. M.-d. (2007). Peroxisome Proliferator-activated Receptor (PPAR)-2 Controls Adipocyte Differentiation and Adipose Tissue Function through the Regulation of the Activity of the Retinoid X Receptor/PPAR{gamma} Heterodimer. J. Biol. Chem. 282: 37738-37746 [Abstract] [Full Text]  
• Perreault, A., Lemieux, C., Bachand, F. (2007). Regulation of the Nuclear Poly(A)-binding Protein by Arginine Methylation in Fission Yeast. J. Biol. Chem. 282: 7552-7562 [Abstract] [Full Text]  
• Wagner, S., Weber, S., Kleinschmidt, M. A., Nagata, K., Bauer, U.-M. (2006). SET-mediated Promoter Hypoacetylation Is a Prerequisite for Coactivation of the Estrogen-responsive pS2 Gene by PRMT1. J. Biol. Chem. 281: 27242-27250 [Abstract] [Full Text]  
• Szatmari, I., Vamosi, G., Brazda, P., Balint, B. L., Benko, S., Szeles, L., Jeney, V., Ozvegy-Laczka, C., Szanto, A., Barta, E., Balla, J., Sarkadi, B., Nagy, L. (2006). Peroxisome Proliferator-activated Receptor {gamma}-regulated ABCG2 Expression Confers Cytoprotection to Human Dendritic Cells. J. Biol. Chem. 281: 23812-23823 [Abstract] [Full Text]