Epigenetic chromatin marks restrict the ability of differentiated cells to change gene expression programs in response to environmental cues and to transdifferentiate. Polycomb group (PcG) proteins mediate gene silencing and repress transdifferentiation in a manner dependent on histone H3 lysine 27 trimethylation (H3K27me3). However, macrophages migrated into inflamed tissues can transdifferentiate, but it is unknown whether inflammation alters PcG-dependent silencing. Here we show that the JmjC-domain protein Jmjd3 is a H3K27me demethylase expressed in macrophages in response to bacterial products and inflammatory cytokines. Jmjd3 binds PcG target genes and regulates their H3K27me3 levels and transcriptional activity. The discovery of an inducible enzyme that erases a histone mark controlling differentiation and cell identity provides a link between inflammation and reprogramming of the epigenome, which could be the basis for macrophage plasticity and might explain the differentiation abnormalities in chronic inflammation.

The histone H3 lysine 27 demethylase Jmjd3 links inflammation to inhibition of polycomb-mediated gene silencing / M.G.T. F. De Santa, E. Prosperini, S. Notarbartolo, G. Testa. - In: CELL. - ISSN 0092-8674. - 130:6(2007), pp. 1083-1094.

The histone H3 lysine 27 demethylase Jmjd3 links inflammation to inhibition of polycomb-mediated gene silencing

S. Notarbartolo
Penultimo
;
G. Testa
Ultimo
2007

Abstract

Epigenetic chromatin marks restrict the ability of differentiated cells to change gene expression programs in response to environmental cues and to transdifferentiate. Polycomb group (PcG) proteins mediate gene silencing and repress transdifferentiation in a manner dependent on histone H3 lysine 27 trimethylation (H3K27me3). However, macrophages migrated into inflamed tissues can transdifferentiate, but it is unknown whether inflammation alters PcG-dependent silencing. Here we show that the JmjC-domain protein Jmjd3 is a H3K27me demethylase expressed in macrophages in response to bacterial products and inflammatory cytokines. Jmjd3 binds PcG target genes and regulates their H3K27me3 levels and transcriptional activity. The discovery of an inducible enzyme that erases a histone mark controlling differentiation and cell identity provides a link between inflammation and reprogramming of the epigenome, which could be the basis for macrophage plasticity and might explain the differentiation abnormalities in chronic inflammation.
NF-kappa-B; embryonic stem-cells; target genes; methyltransferase complex; developmental regulators; bone-formation; methylation; chromatin; proteins; transdetermination
Settore BIO/11 - Biologia Molecolare
Article (author)
File in questo prodotto:
File Dimensione Formato  
1-s2.0-S0092867407010823-main.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 1.25 MB
Formato Adobe PDF
1.25 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/65852
Citazioni
  • ???jsp.display-item.citation.pmc??? 403
  • Scopus 716
  • ???jsp.display-item.citation.isi??? 685
social impact