Figure 8

A schematic diagram illustrating the major components involved in REST-mediated local chromatin remodeling and their relationships to our findings. (a) RE1 is initially covered by a nucleosome. (b) A yet-to-identified cellular mechanism initiates nucleosome repositioning with the assistance of BRG1, resulting in the exposure of the RE1 motif and the subsequent occupation of it by REST. The exact sequential order is not clear to date. (c) With the assistance of mSin3 and coREST, the RE1-bound REST complexes then recruit histone deacetylases (HDACs) to promote histone deacetylations, histone methylases (G9a, PRC2) to increase methylations on H3K9 and H3K27, and histone demethylases (LSD1, SMCX) to reduce methylations on H3K4. The presence of PRC2 in REST complexes is unknown but suggested by our analysis, so we have drawn a dashed line around it. Our data also strongly suggest that REST can recruit additional histone methylases and demethylases (represented by question marks) to target other lysine residues of histones, which display RE1/REST-dependent changes in the current study. The enumeration of all the histone modifying enzymes in the REST complexes will enhance our comprehension of how the complicated histone modifications are established; then, more investigations will be needed to decipher how these modifications cross-talk and orchestrate the regulation of RE1 genes.