發佈日期：2021-06-10 ∣ 演講
本中心永久會員林劭品教授邀請到 University of Cambridge 的 Dr. Miguel Constância，於6/
此外，林教授現擔任 “Frontiers in Cell and Developmental Biology” (IF: 5.186; 6/41 in Developmental Biology) 客座編輯，負責主題為“Legacies of Epigenetic Perturbations”，
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Epigenetic programming of growth and metabolic health across the life-course
Miguel Constancia, Metabolic Research Laboratories and Department of Obstetrics and Gynaecology, University of Cambridge
The epigenome is the set of chemical tags added to the DNA and DNA-associated proteins in chromatin, which alter gene expression and are heritable (via mitosis but also meiosis). These chemical modifications occur as a natural process in development and tissue differentiation, broadly known as epigenetic programming, and can be altered in response to environmental exposures or disease (e.g., epimutations).
A paradigm of epigenetic phenomena is represented by genomic imprinting. Imprinted genes are the only genes in the mammalian genome that retain information regarding their parental origin. Parent-specific ‘memory’ is mainly achieved by the addition of methyl groups to DNA sequences at, or nearby, imprinted genes in a germline-specific manner (i.e., oocyte and sperm DNA are differentially marked). Inheritance of these methylation marks in the offspring result in epigenetic silencing of one of the parental alleles and monoallelic expression.
The Insulin/Insulin-like growth factor (INS/IGF) signalling pathway is an evolutionarily conserved growth and metabolic pathway in mammals. Interestingly, two family gene members, IGF2 (Insulin-like growth factor 2) and IGF2R (Insulin-like growth factor type II receptor) are imprinted, i.e., paternally and maternally expressed genes, respectively. Moreover, IGF2 is located within the so-called Imprinting Growth Cluster, which contains a number of clustered imprinted genes that play key roles in placental development and fetal growth, in both mouse and human. During this talk, I will discuss the epigenetic regulation at this growth cluster and how de-regulation, either by epimutations or genetic deletions, impacts on programming of growth, health and disease. Altered epigenetic programming is an important contributing mechanism to adverse pregnancy outcomes, from gestational diabetes and fetal growth restriction, to susceptibility risk of disease in later life, such as type 2 diabetes, obesity and cardiovascular disease. Specifically, I will discuss two key developmental biology questions that our research on the INS/IGF pathway is addressing: 1. how fetal growth is coordinated with placental growth and function, and 2. how fetal genes affect maternal metabolism, and the implications for the health of the mother and offspring across the life-course.
Dr. Neil Youngson (n.youngson@researchinliver.