Arginine methylation provides epigenetic transcription memory for retinoid-induced differentiation in myeloid cells

Balint L. Balint, Attila Szanto, Andras Madi, Uta Maria Bauer, Petra Gabor, Szilvia Benko, Laszlo G. Puskás, Peter J.A. Davies, Laszlo Nagy

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)5648-5663
Number of pages16
JournalMolecular and cellular biology
Issue number13
StatePublished - Jul 2005
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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