Fig. 7: Two models explaining the complex regulation of fMyh genes by the shared SE.
The SE is composed of seven enhancer elements (1–7) recruiting TF and cofactors allowing the nuclear formation of a phase separation condensate in myonuclei and allowing robust fMyh expression, adapted from Sabari et al.16. Left, in the hub model even the inactive promoters at the locus are associated in the phase-separated droplet in Myh4 + myonuclei. Right, in the competition/exclusion model, Myh2, Myh1, Myh8, and Myh13 are excluded from the phase-separated droplet in Myh4 + myonuclei because they are not bound by sufficient amount of TF and cofactors. In those myonuclei robust bi-allelic expression of Myh4 is achieved, while transcription of the other genes is not detected10. In this competition/exclusion model, the deletion of Myh1 and Myh4 could lead to the maintenance of Myh8 expression through development in specific muscles, (while in others Myh13 is activated (not represented)) due to the absence of competition by Myh4 or Myh1 promoters. Linc-Myh spans enhancers 3–5. The models are not to scale.
