Fig. 2

Regulation of the myogenin gene control the transition from proliferative myoblasts to differentiated myocytes. To block MyoG expression and prevent early differentiation, a repressive function of MYOD1 is needed. In this repressive action, MYOD1 is recruited on the promoter and is bound by KDMT1A thanks to P38γ phosphorylation at its Ser199 and 200. MYOD1 forms a poised complex with MEF2D, KAP1, G9a, and HDAC. Histone acetyltransferase P300/CAF proteins can also bind to MYOD1/MEF2D complex, but their functions are limited. During induction of differentiation, MYOD1 functions change to allow Myog gene expression. This transition is due to phosphorylation of KAP1, which leads to removal of HDAC1 and G9a proteins from MYOD1/MEF2D complex. In this state, P38α phosphorylates MEF2D at its threonine 308 and 305, which leads to the recruitment of ASH2L and trimethylation of H3K4. At the same time JDP2, JUN and SETD7 are recruited at p300/CAF proteins to allow the establishment of permissive marks H3K4me1 and H3K27/18Ac at the enhancer of Myog and the H3K4me1 mark works as an antagonist to the addition of H3K9me3 by SuV39h1. At the promoter, the MLL/TrxG complex is recruited by MyoD to dimethylate H3R8. In addition, the repressive marks H3K9me2/3 and H3K27me3 are removed by JMJD1c and JMJD2 (KDM6A), respectively, while permissive marks, H3K4me3, H3K36me3, H3R8me2, and H3K27/18Ac, are added at the promoter by MLL2, SETD2, PRMT5, and p300. The presence of these permissive marks allows the recruitment of RNA polymerase II and starting of transcription. At the Myog gene, P38α is responsible of the phosphorylation of MEFD2 as well as of P18 Hamlet (a subunit of SNF2); this phosphorylation leads to the incorporation of unstable H2A.Z variant at the core gene to facilitate transcription