"Puberty is under the control of complex regulatory mechanisms that are sensitive to endogenous factors and environmental cues; metabolic signals and body energy stores being key modifiers of puberty onset. While the mechanisms underlying puberty have been widely studied, our knowledge of its neurohormonal and molecular regulators remains incomplete. Compelling, but still fragmentary, evidence is emerging that epigenetic regulatory mechanisms participate in the dynamic coordination of the cascade of molecular events that leads to puberty; however, conclusive proof of their nature and physiological relevance is still missing. This project aims to characterize the mechanisms, molecular targets and functional relevance of the epigenetic regulation of puberty. Special emphasis will be paid to elucidate the role of epigenetic mechanisms in the control of expression of essential puberty-activating genes, such as Kiss1 and NKB, and their eventual interaction with members of the Polycomb group of transcriptional silencers, whose role in puberty has been recently proposed. In addition, a multi-disciplinary approach will be implemented to define the role of epigenetic changes in the metabolic control of puberty, with attention to conditions of precocious puberty due to early-onset obesity. In doing so, this project will significantly enhance our knowledge of the molecular mechanisms responsible for the control of puberty, and will define to what extend epigenetics may contribute to define pubertal timing in general, and its metabolic regulation in particular; issues of significant translational interest given the increasing trends of disorders of puberty and their potential link to the rapid rise of metabolic alterations in children. In addition to its scientific value, this project is provided of considerable formative contents, thus fostering the prospect of the fellow to pursue his independent scientific career and of collaborations between the out-going and return groups."