In our opening lecture, we will begin by asking the question, 'why is it that your neurons are completely different than your skin or muscle cells, yet all three cell types contain the same DNA?'. To begin to answer this question, I will introduce the field of "Epigenetics", defined as the study of heritable changes in gene expression that are not regulated by the DNA nucleotide sequence. Check out these videos: http://www.youtube.com/watch?v=eYrQ0EhVCYA and http://www.youtube.com/watch?v=Fj4d-9Jgl6g
This lecture will start in the mid-1990's with the discovery of the first histone modification enzymes, the histone acetyltransferases and histone deacetylases. We will then go on to outline the ever-expanding array of enzymatic activities such as acetylation, phosphorylation, methylation, ubiquitinylation, and explore the enzymes involved and their mechanisms of action in gene expression control.
This lecture will introduce the Polycomb and Trithorax group proteins. A multitude of studies, in different organisms, have firmly established the vital and conserved roles of these epigenetic modifiers in development and in stem and progenitor cell differentiation. This lecture will focus on how these proteins function on a molecular level to "lock" cellular identity.
This lecture will focus on the process of DNA methylation. We will outline the enzymes involved (DNA methyltransferases) and the mechanisms by which they regulate gene expression. We will also review current research questions in this field such as how DNA methyltransferases are recruited to DNA.
This lecture will discuss the rapidly advancing field of non-coding RNAs (ncRNA) and describe their emerging roles in gene expression control. We will highlight two examples, namely the Xist long ncRNA which regulates X-chromosome inactivation and the newly identified HOTAIR long ncRNA which regulates homeotic (HOX) gene transcription.
This lecture will attempt to put what we have learnt in the previous five lectures together in order to explain, at a molecular level, how cells specify their identity during both development and differentiation. We will also explore the role of the various epigenetic modifiers in X-chromosome inactivation and in imprinting, the phenomenon by which certain genes are expressed in a parent-of-origin-specific manner.
Today we will ask the rather strange question, "Can a ball roll up a hill?". We will explore how epigenetics is at the heart of cellular reprogramming, currently being exploited in regenerative medicine, most notably with the advent of induced pluripotent stem cells (iPS). We will give examples of how our improving understanding of these molecular events is already contributing to new and improved methods of cellular reprogramming.
This lecture will focus on the importance of epigenetics in human disease. Until recently, the study of human disease has largely focused on genetic mechanisms. However, disruption of epigenetic modifiers have been shown to cause several major pathologies, including cancer. We will explore several examples and highlight the recent development of new diagnostic tools to reveal epigenetic alterations and the "epigenetic drugs" that are in clinical trials for the treatment of cancer.