Arginine Methylation Provides Epigenetic Transcription Memory for Retinoid-Induced Differentiation in Myeloid Cells
Autor: | Attila Szanto, Balint L. Balint, László G. Puskás, András Mádi, Peter J.A. Davies, Laszlo Nagy, Uta-Maria Bauer, Petra Gabor, Szilvia Benko |
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Jazyk: | angličtina |
Rok vydání: | 2005 |
Předmět: |
Genetic Markers
Protein-Arginine N-Methyltransferases Epigenetic regulation of neurogenesis Transcription Genetic Hydrolases Cellular differentiation Gene Expression HL-60 Cells Biológiai tudományok Biology Arginine Models Biological Epigenesis Genetic Histones Retinoids Epigenetics of physical exercise Protein-Arginine Deiminase Type 4 Természettudományok Gene expression Humans Cell Lineage Myeloid Cells Epigenetics Promoter Regions Genetic Molecular Biology Epigenomics Regulation of gene expression Transglutaminases Ionophores Acetylation Cell Differentiation Cell Biology DNA Methylation Molecular biology Chromatin Cell biology Gene Expression Regulation DNA methylation Protein-Arginine Deiminases |
Popis: | 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, pre-acetylation, 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. |
Databáze: | OpenAIRE |
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