Tceal7 is a BRG1-regulated target of calcineurin signaling that promotes myoblast differentiation

The transcriptional control of skeletal muscle differentiation requires the coordinated activity of lineage-defining transcription factors, signal-responsive regulators, chromatin modifiers, and ATP-dependent chromatin remodeling enzymes. Here, we identify TCEAL7, a member of the X-linked, poorly characterized TCEAL family of proteins, as a direct downstream target of BRG1-containing mammalian SWI/SNF (mSWI/SNF) complexes and calcineurin signaling during myoblast differentiation. Analyses of previously published datasets showed that pharmacological inhibition of mSWI/SNF bromodomains or knockdown of the BRG1 ATPase, but not knockdown of the homologue BRM ATPase, significantly reduced Tceal7 expression in differentiating C2C12 myoblasts. We demonstrate that BRG1 occupancy at the Tceal7 promoter increased during differentiation, paralleling the induction of Tceal7 expression and nuclear accumulation of TCEAL7 protein. BRG1 functions in part by integrating calcium-dependent cues via the phosphatase calcineurin (Cn); we also determined that Cn knockdown or pharmacological inhibition of Cn suppressed Tceal7 expression and impaired myoblast differentiation. The data suggest that both BRG1-driven chromatin remodeling and Cn signaling converge on Tceal7 regulation. Functionally, Tceal7 knockdown altered cell proliferation and disrupted myoblast differentiation, at least in part due to reduced expression of Myogenin , which encodes a transcription factor that is an essential differentiation determinant. RNA-seq analysis revealed broad dysregulation of myogenic, metabolic, and cell-cycle gene programs in Tceal7 -deficient cells, including changes in cyclin-dependent kinase-regulated pathways consistent with prior reports linking TCEAL7 to cell-cycle control. Together, these findings identify TCEAL7 as a necessary component of the myogenic regulatory network whose expression is controlled by BRG1-dependent chromatin remodeling and Cn activity.