Combinatorial, site-specific requirement for heterochromatic silencing factors in the elimination of nucleosome-free regions.

High-resolution nucleosome occupancy maps of heterochromatic regions of wild-type and silencing-defective mutants of the fission yeast Schizosaccharomyces pombe revealed that heterochromatin induces the elimination of nucleosome-free regions (NFRs). NFRs associated with transcription initiation sites as well as those not associated with promoters are affected. We dissected the roles of the ...
histone H3K9 methyltransferase Clr4 and the HP1 proteins Swi6 and Chp2, as well as the two catalytic activities of the SHREC histone deacetylase (HDAC)/ATPase effector complex. Strikingly, different DNA sites have distinct combinatorial requirements for these factors: Five classes of NFRs were identified that are eliminated by silencing factors through a mechanistic hierarchy governed by Clr4. The SHREC HDAC activity plays a major role in the elimination of class I-IV NFRs by antagonizing the action of RSC, a remodeling complex implicated in NFR formation. We propose that heterochromatin formation involves the deployment in several sequence-specific mechanisms to eliminate gaps between nucleosomes, thereby blocking access to the DNA.
Mesh Terms:
Cell Line, Tumor, DNA-Binding Proteins, Down-Regulation, Gene Expression Regulation, Histones, Humans, Neoplasm Proteins, Nuclear Proteins, Oncogenes, Oxidoreductases, N-Demethylating, Protein Binding, Protein Processing, Post-Translational, Repressor Proteins, Trans-Activators, Transcription Factors
Genes Dev.
Date: Aug. 15, 2010
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