TY - JOUR
T1 - Arginine methylation provides epigenetic transcription memory for retinoid-induced differentiation in myeloid cells
AU - Balint, Balint L.
AU - Szanto, Attila
AU - Madi, Andras
AU - Bauer, Uta Maria
AU - Gabor, Petra
AU - Benko, Szilvia
AU - Puskás, Laszlo G.
AU - Davies, Peter J.A.
AU - Nagy, Laszlo
PY - 2005/7
Y1 - 2005/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=20744442981&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=20744442981&partnerID=8YFLogxK
U2 - 10.1128/MCB.25.13.5648-5663.2005
DO - 10.1128/MCB.25.13.5648-5663.2005
M3 - Article
C2 - 15964820
AN - SCOPUS:20744442981
SN - 0270-7306
VL - 25
SP - 5648
EP - 5663
JO - Molecular and cellular biology
JF - Molecular and cellular biology
IS - 13
ER -