Myogenin is required for assembly of the transcription machinery on muscle genes during skeletal muscle differentiation

Abstract

Skeletal muscle gene expression is governed by the myogenic regulatory family (MRF) which includes MyoD (MYOD1) and myogenin (MYOG). MYOD1 and MYOG are known to regulate an overlapping set of muscle genes, but MYOD1 cannot compensate for the absence of MYOG in vivo. In vitro, late muscle genes have been shown to be bound by both factors, but require MYOG for activation. The molecular basis for this requirement was unclear. We show here that MYOG is required for the recruitment of TBP and RNAPII to muscle gene promoters, indicating that MYOG is essential in assembling the transcription machinery. Genes regulated by MYOD1 and MYOG include genes required for muscle fusion, myomaker and myomerger, and we show that myomaker is fully dependent on activation by MYOG. We also sought to determine the role of MYOD1 in MYOG dependent gene activation and unexpectedly found that MYOG is required to maintain Myod1 expression. However, we also found that exogenous MYOD1 was unable to compensate for the loss of Myog and activate muscle gene expression. Thus, our results show that MYOD1 and MYOG act in a feed forward loop to maintain each other’s expression and also show that it is MYOG, and not MYOD1, that is required to load TBP and activate gene expression on late muscle gene promoters bound by both factors.

Identification of Robust and Key Differentially Expressed Genes during C2C12 Cell Myogenesis Based on Multiomics Data

“…These results indicate that the cooperative binding of KLF5 increases H3K27ac levels at the binding sites of these three myogenic factors. Previous research revealed that MYOD, MYOG, and MEF2D sequentially play a role in myogenesis [ 38 , 49 , 50 , 51 ]. We tried to simulate the assembly process of the enhancer transcription machinery during myogenesis.…”

“…However, their functions are distinct. MYOD first induces chromatin modification, and then MYOG binds to activate gene expression [ 50 , 51 ]. MEF2D lacks independent myogenic activity and requires cooperation with MRF family members to activate the myogenic differentiation program [ 68 ].…”

Tent5a modulates muscle fiber formation in adolescent idiopathic scoliosis via maintenance of myogenin expression

“…Rather than MyoD, late maturation depends mainly on myogenin, and MyoD cannot compensate for the loss of myogenin in vivo. 53 In addition to controlling the maturation of skeletal muscle, myogenin also affected the location and distribution of resident satellite cells, which demonstrated a multilevel contribution of myogenin to muscle homeostasis throughout life. 54 Therefore, the poly(A) polymerase Tent5a might play an important role in maintaining the mRNA stability of myogenin.…”

Chondroitin sulfate E downregulates N-cadherin and suppresses myotube formation

“…In fact, it has been reported that knockout of myomaker and myomixer suppressed the formation of MyHC-positive multinucleated myotubes, which is consistent with our results [ 34 ]. The gene expression of proteins involved in membrane fusion, including myomaker and myomixer, is regulated by myogenin, which is known to bind to the promoter region of these genes and enhance gene expression [ 1 , 11 , 19 ]. In addition, myogenin is a muscle-specific transcription factor regulated by N-cadherin-mediated intracellular signaling, and N-cadherin inhibitors have been found to decrease myogenin protein expression in C2C12 cells [ 6 ].…”