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

Abstract:

: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.

journal_name

Mol Cell Biol

authors

Balint BL,Szanto A,Madi A,Bauer UM,Gabor P,Benko S,Puskás LG,Davies PJ,Nagy L

doi

10.1128/MCB.25.13.5648-5663.2005

subject

Has Abstract

pub_date

2005-07-01 00:00:00

pages

5648-63

issue

13

eissn

0270-7306

issn

1098-5549

pii

25/13/5648

journal_volume

25

pub_type

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