Abstract

In vertebrates, the somatotropic axis comprising the pituitary gland, liver and muscle plays a major role in myogenesis. Its output in terms of muscle growth is highly affected by nutritional and environmental cues, and thus likely epigenetically regulated. Hydroxymethylation is emerging as a DNA modification that modulates gene expression but a holistic characterization of the hydroxymethylome of the somatotropic axis has not been investigated to date. Using reduced representation 5-hydroxymethylcytosine profiling we demonstrate tissue-specific localization of 5-hydroxymethylcytosines at single nucleotide resolution. Their abundance within gene bodies and promoters of several growth-related genes supports their pertinent role in gene regulation. We propose that cytosine hydroxymethylation may contribute to the phenotypic plasticity of growth through epigenetic regulation of the somatotropic axis.

Highlights

  • Somatic growth requires a well-tuned transcriptional synchroniza­ tion of three main tissue types that compose the somatotropic axis: the pituitary gland, liver and skeletal muscle

  • Somatic growth and normal development are regulated by a complex molecular cascade that is affected by several mechanisms, including epigenetic modifications

  • We show that DNA hydroxymethylation is present throughout the genome, is characterized by tissue-specific profiles and is highly enriched within gene bodies (Fig. 6)

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Summary

Introduction

Somatic growth requires a well-tuned transcriptional synchroniza­ tion of three main tissue types that compose the somatotropic axis: the pituitary gland, liver and skeletal muscle. From the production of growth hormone (GH) in the pituitary gland to the stimulation and regulation of hundreds of genes in the liver and muscle, the somato­ tropic axis plays a critical role across several biological pathways involved in somatic growth, carbohydrate and lipid metabolism, energy equilibrium, normal development and reproduction [1,2,3]. The liver is the main source of igf production; in cases of malnutrition the liver is predominantly unresponsive to GH stimulation [10]. Such interactions have been widely demonstrated and both endocrine and paracrine igf have been linked to bone, cartilage and muscle growth across vertebrates [11]

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