Project description:Heterochromatin, a highly compact chromatin state characterized by histone H3 lysine 9 methylation (H3K9me) and HP1 protein binding, epigenetically silences the underlying DNA and influences the expression of neighboring genes. Therefore the sites of heterochromatin assembly and its subsequent spreading are generally precisely determined. Here we show that in fission yeast, the combined absence of anti-silencing factors Mst2 and Epe1 results in uncontrolled heterochromatin spreading and severe growth defects. Interestingly, these cells quickly recover by accumulating H3K9me at the clr4+ locus, which encodes the H3K9 methyltransferase essential for heterochromatin assembly, thereby leading to reduced expression of Clr4 to restrain heterochromatin spreading. Preventing H3K9me at the clr4+ locus resulted in the accumulation of H3K9me at the rik1+ locus, which encodes another component of the Clr4 complex essential for H3K9me. Our results demonstrate that promiscuous heterochromatin assembly enables fast adaptation in response to changes in chromatin landscape and illustrate a negative feedback mechanism by which cells counteract toxic heterochromatin accumulation.
Project description:Snf2 Family Protein Fft3 Suppresses Nucleosome Turnover to Promote Epigenetic Inheritance of Heterochromatin and Proper Replication of the Genome [BrdU IP]
Project description:Snf2 Family Protein Fft3 Suppresses Nucleosome Turnover to Promote Epigenetic Inheritance of Heterochromatin and Proper Replication of the Genome [H3K9me2 ChIP]
Project description:Proteins of the conserved HP1 family are elementary components of heterochromatin and are generally assumed to play a central role in creating a rigid heterochromatic network that is densely packed and inaccessible to the transcription machinery. In this study we demonstrate that the fission yeast HP1 protein Swi6 exists as a single highly dynamic population and rapidly exchanges in cis and in trans between different heterochromatic regions. Binding to methylated H3K9 or to heterochromatic RNA decelerates Swi6 mobility. We further show that Swi6 is largely dispensable to maintain heterochromatin domains. In contrast, our results disclose an unexpected role of Swi6 in demarcating constitutive heterochromatin from neighboring euchromatin. Our results are consistent with a stochastic model of heterochromatin and imply that heterochromatin is permissive for transcription throughout the cell cycle. Rather than promoting maintenance and spreading of heterochromatin, Swi6 appears to limit these processes to ensure that heterochromatin is appropriately confined.