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Maternal protein restriction during pregnancy induces CCAAT/enhancer-binding protein (C/EBPβ) expression through the regulation of histone modification at its promoter region in female offspring rat skeletal muscle

Maternal nutrition during pregnancy is an important intrauterine environmental factor that can cause persistent alterations of the offspring genome and is associated with potential disease risk later in life. In the present study, we investigated the impact of a maternal low protein diet (LP) on the expression of the transcription factor CCAAT/enhancer-binding protein (C/EBPβ) in offspring skeletal muscle. C/EBPβ belongs to a family of transcription factors that regulates the expression of genes involved in energy homeostasis and muscle development. We investigated C/EBPβ transcriptional regulation from an epigenetic aspect. We observed sex-dependent differences in C/EBPβ expression in offspring skeletal muscle subjected to a maternal protein-restricted diet. In female offspring skeletal muscle, both C/EBPβ mRNA and protein levels were increased by maternal protein restriction. However, C/EBPβ expression was not altered in other tissues or male offspring. Analysis of transcriptional and epigenetic regulation showed acetylated histone 3 and acetylated histone 4 at significantly increased levels at the C/EBPβ promoter region in female LP pup's muscle. Phosphoenolpyruvate carboxykinase (PEPCK) gene transcription was also up-regulated in female LP pups through the increased binding of C/EBPβ at its promoter. The induction of C/EBPβ expression in female offspring skeletal muscle by maternal protein restriction during pregnancy may indicate C/EBPβ involvement in signaling response in energy metabolism to a low maternal protein diet.