Gene silencing in budding yeast

Published on October 1, 2007 Updated on August 31, 2016   51 min

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Hello, I'm Susan Gasser. And I'm going to you speak to you today about Gene Silencing in Budding Yeast.
Gene silencing is an epigenetic phenomenon whereby a gene is silenced or not transcribed in a manner that is heritable from one cell to the next. In the lower right-hand corner, you see colonies of yeast where a gene that will turn the yeast cell red is either expressed or not expressed in these colonies. The sectoring shows heritable repression. The same phenomenon occurs in the eye of the Drosophila when a gene is transferred or emplaced near centromeric head or chromatin. Today, I'll explain how this phenomenon occurs.
First of all, our genome is made-up of DNA complexed with histone proteins in a complex called chromatin. This protein DNA complex carries an additional level of organization and information in an epigenome. When the histone tails are acetylated or transcription factors are bound, we call this euchromatin, it's accessible and plastic to transcription machinery and usually transcriptionally active. On the other hand, if the histone tails are methylated, the other proteins bind, turning this chromatin into heterochromatin. It is inaccessible. It shows restricted expression and can be inherited in a silent state.
The active chromatin is composed of a number of modifications across all species correlated with active genes. Histone H3 can be methylated on lysine 4, on lysine 36, and the histone H4 tail can be acetylated on a number of lysine residues. These modifications attract nucleosome remodelers which they can shift or evict nucleosomes, and finally, is the binding of proteins that keep the domain in an active state. In repressed chromatin, histone tails are modified with other kinds of modifications. Histone H3 is modified by methylation on lysine 9 or lysine 27, and histone H4 on lysine 20. These methylation sites can attract repressive proteins that then mask the DNA polymerases from the activity of transcription. In higher eukaryotes, cytosine residues become methylated and this correlates with a repressed state as well as the stable binding of general repressors. Finally, in some species, double-stranded RNAs are transcribed from heterochromatic regions and this again nucleates repression of the genes. In budding yeast, which we'll be talking about today, all the modifications here listed are present and they're conserved from yeast to man. The phenomenon, however, of active or inactive chromatin is largely the same. So why should we study silent heterochromatin in a small organism like budding yeast?