Activation of SRF-regulated chromosomal templates by Rho-family GTPases requires a signal that also induces H4 hyperacetylation.
Constitutively active forms of the small GTPases RhoA (RhoA.V14) and Cdc42 (Cdc42.V12) induce expression of extrachromosomal SRF reporter genes in microinjection experiments, but only Cdc42.V12 can efficiently activate a chromosomal template. Both SAPK/JNK-dependent or -independent signals can cooperate with RhoA.V14 to activate chromosomal SRF reporters, and it is SAPK/JNK activation by Cdc42.V12 that allows it to activate chromosomal templates. Cooperating signals can be bypassed by deacetylase inhibitors. Three findings show that histone H4 hyperacetylation is one target for cooperating signals, although it alone is not sufficient: (1) Cdc42.V12, but not RhoA.V14, induces H4 hyperacetylation; (2) cooperating signals use the same SAPK/JNK-dependent or -independent pathways to induce H4 hyperacetylation; (3) growth factor and stress stimuli induce substantial H4 hyperacetylation, detectable in reporter gene chromatin. These data establish a link between signal-regulated acetylation events and gene transcription.
Alberts
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AS
Transcription Laboratory, Imperial Cancer Research Fund, London, United Kingdom.
Geneste
O
O
Treisman
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D016475:3T3 Cells; D000107:Acetylation; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D002875:Chromosomes / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000235:genetics*; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D017930:Genes, Reporter; D016762:Genes, fos / Q000235:genetics*; D006657:Histones / Q000378:metabolism*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases; D009687:Nuclear Proteins / Q000235:genetics*; D026362:Serum Response Factor; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics; D020764:cdc42 GTP-Binding Protein; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae; D048051:p38 Mitogen-Activated Protein Kinases; D020742:rhoA GTP-Binding Protein
D018797:Cell Cycle Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; D009687:Nuclear Proteins; D026362:Serum Response Factor; D014157:Transcription Factors; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D020764:cdc42 GTP-Binding Protein; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae; D020742:rhoA GTP-Binding Protein