Histone crosstalk between H3S10ph and H4K16ac generates a histone code that mediates transcription elongation.
The phosphorylation of the serine 10 at histone H3 has been shown to be important for transcriptional activation. Here, we report the molecular mechanism through which H3S10ph triggers transcript elongation of the FOSL1 gene. Serum stimulation induces the PIM1 kinase to phosphorylate the preacetylated histone H3 at the FOSL1 enhancer. The adaptor protein 14-3-3 binds the phosphorylated nucleosome and recruits the histone acetyltransferase MOF, which triggers the acetylation of histone H4 at lysine 16 (H4K16ac). This histone crosstalk generates the nucleosomal recognition code composed of H3K9acS10ph/H4K16ac determining a nucleosome platform for the bromodomain protein BRD4 binding. The recruitment of the positive transcription elongation factor b (P-TEFb) via BRD4 induces the release of the promoter-proximal paused RNA polymerase II and the increase of its processivity. Thus, the single phosphorylation H3S10ph at the FOSL1 enhancer triggers a cascade of events which activate transcriptional elongation.
Zippo
Alessio
A
Dipartimento di Biologia Molecolare Università di Siena, Siena, Italy.
Serafini
Riccardo
R
Rocchigiani
Marina
M
Pennacchini
Susanna
S
Krepelova
Anna
A
Oliviero
Salvatore
S
D000818:Animals; D002460:Cell Line; D042863:Cyclin-Dependent Kinase 9 / Q000378:metabolism; D004330:Drosophila; D036681:Fluorescence Recovery After Photobleaching; D031541:Fluorescence Resonance Energy Transfer; D042421:Histone Code; D006657:Histones / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009707:Nucleosomes / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D015003:Yeasts; D000099169:Fos-Related Antigen 1
D042863:Cyclin-Dependent Kinase 9; D006657:Histones; D009707:Nucleosomes; D016760:Proto-Oncogene Proteins c-fos; D014157:Transcription Factors; D000099169:Fos-Related Antigen 1