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 Bioljournal_title
Molecular and cellular biologyauthors
Balint BL,Szanto A,Madi A,Bauer UM,Gabor P,Benko S,Puskás LG,Davies PJ,Nagy Ldoi
10.1128/MCB.25.13.5648-5663.2005subject
Has Abstractpub_date
2005-07-01 00:00:00pages
5648-63issue
13eissn
0270-7306issn
1098-5549pii
25/13/5648journal_volume
25pub_type
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