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Intergenic transcripts regulate the epigenetic state of rRNA genes.
Christine Mayer1, Kerstin-Maike Schmitz, Junwei Li
1German Cancer Research Center, Division of Molecular Biology of the Cell II, D-69120 Heidelberg, Germany.
Molecular Cell
|May 9, 2006
Summary
Intergenic spacer (IGS) transcripts are essential for maintaining rDNA gene chromatin structure. These transcripts interact with TIP5, a component of the NoRC complex, to regulate heterochromatin formation and gene transcription.
Area of Science:
- Epigenetics
- Molecular Biology
- Chromatin Biology
Background:
- Transcripts from the intergenic spacer (IGS) of ribosomal DNA (rDNA) have been known for 20 years, but their function remains largely uncharacterized.
- The biological role of IGS transcripts in regulating rDNA gene expression and chromatin structure is poorly understood.
Purpose of the Study:
- To elucidate the biological role of IGS transcripts in the epigenetic regulation of rDNA arrays.
- To investigate the mechanism by which IGS transcripts establish and maintain heterochromatin at rDNA promoters.
Main Methods:
- Investigated the interaction between TIP5, the NoRC complex, and IGS transcripts using RNA-binding assays.
- Utilized site-directed mutagenesis to disrupt TIP5 RNA-binding capabilities.
- Performed knockdown experiments of IGS transcripts.
- Assessed H3K9&H4K20 methylation, HP1 recruitment, NoRC localization, DNA methylation, and rDNA transcription levels.
Main Results:
- IGS transcripts are required for establishing and maintaining heterochromatin at a subset of rDNA array promoters.
- TIP5's interaction with IGS transcripts is crucial for NoRC association with rDNA, H3K9&H4K20 methylation, and HP1 recruitment.
- Knockdown of IGS transcripts disrupts NoRC's nucleolar localization, reduces DNA methylation, and increases rDNA transcription.
Conclusions:
- Processed IGS transcripts play a critical role in the epigenetic control of the rDNA locus.
- IGS transcripts are essential mediators of chromatin structure and heterochromatin formation at rDNA genes.