Muscles cannot break a NuRDy heart

Abstract

The recent article from Gómez‐del Arco et al (2016) in Cell Metabolism reveals the essential role of chromodomain‐helicase‐DNA‐binding protein 4 (CHD4) in the control of alternative gene expression in cell types that share seemingly redundant, yet distinct, biological properties, such as the contractile activities of striated cardiac or skeletal muscles. An altered expression of genes for alternative sarcomeric and metabolic programs occurred upon genetic inactivation of Chd4 in skeletal or cardiac cells, leading to formation of “hybrid” striated muscles and pathological outcomes.

Figure 1. CHD4 coordinates gene expression in striated muscles to prevent formation of “hybrid” pathological contractile tissues

Heart (left) and skeletal myofibers (right) express cardiac‐specific genes (orange rectangle) and skeletal muscle‐specific genes (purple rectangle), respectively, in a mutually exclusive way. This tissue‐specific pattern of gene expression depends on the integrity of the chromodomain‐helicase‐DNA‐binding protein (Chd4)‐containing NuRD complex that represses alternative transcription of skeletal muscle genes in heart and vice versa. In the absence of CHD4, de‐repression of target genes causes inappropriate expression of alternative genes that interfere with tissue function and leads to pathological outcomes.