Molecular Analysis of the Inheritance of Transcriptional Silencing
Abstract
Silent chromatin domains prevent transcription by packaging DNA into a higher order heterochromatin structure that is inaccessible to the transcriptional machinery. To preserve the transcriptional program in dividing cells, silent and active chromatin domains must be faithfully inherited during chromosome replication and segregation. A failure to propagate set transcriptional programs can drastically change gene expression programs, resulting in a variety of diseases and cancers. In this study, we use the budding yeast, Saccharomyces cerevisiae, to understand how proliferating cells inherit defined chromatin states. We identified, for the first time, two proteins, Sir1 and Asf1, specifically required for the inheritance of transcriptional silencing. We also generated conditional alleles of these inheritance proteins and show that our conditional alleles separate the inheritance process into two fundamental steps: S phase dependent disruption followed by active restoration. These fundamental findings allow us to further dissect and understand the process of epigenetic inheritance, enabling us to devise novel treatments against cancers arising from aberrant gene silencing.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2007
- Accession Number
- ADA483245
Entities
People
- Leslie E. Chu
Organizations
- University of California, San Francisco