Dynamic changes in histone H3 Lys 9 methylation occurring at tightly regulated inducible inflammatory genes.
Methylation of histone H3 at Lys 9 is causally linked to formation of heterochromatin and to long-term transcriptional repression. We report an unexpected pattern of H3 Lys 9 methylation occurring at a subset of inducible inflammatory genes. This pattern is characterized by relatively low constitutive levels of H3 Lys 9 methylation that are erased upon activation and restored concurrently with post-induction transcriptional repression. Changes in H3 Lys 9 methylation strongly correlate with RNA polymerase II recruitment and release. In particular, remethylation correlates with RNApolII release more strongly than does histone deacetylation. We propose that, by generating a window of time in which transcription is permitted, dynamic modulation of H3 Lys 9 methylation adds an additional regulatory level to transcriptional activation of tightly controlled inducible genes.
Institute for Research in Biomedicine, Via Vela 6, CH6501, Bellinzona, Switzerland.
Simona
S
Saccani
Gioacchino
G
Natoli
D002478:Cells, Cultured; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000235:genetics; D003713:Dendritic Cells / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006657:Histones / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008239:Lysine / Q000737:chemistry; D008745:Methylation; D011401:Promoter Regions, Genetic; D012319:RNA Polymerase II / Q000378:metabolism; D015533:Transcriptional Activation
C515460:CCL19 protein, human; C515478:CCL21 protein, human; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D019742:Chemokines, CC; D006657:Histones; D008070:Lipopolysaccharides; D012319:RNA Polymerase II; D008239:Lysine