<i>Tceal7</i> 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 <i>Tceal7</i> expression in differentiating C2C12 myoblasts. We demonstrate that BRG1 occupancy at the <i>Tceal7</i> promoter increased during differentiation, paralleling the induction of <i>Tceal7</i> 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 <i>Tceal7</i> expression and impaired myoblast differentiation. The data suggest that both BRG1-driven chromatin remodeling and Cn signaling converge on <i>Tceal7</i> regulation. Functionally, <i>Tceal7</i> knockdown altered cell proliferation and disrupted myoblast differentiation, at least in part due to reduced expression of <i>Myogenin</i>, 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 <i>Tceal7</i>-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.