CHD7 Targets Active Gene Enhancer Elements to Modulate ES Cell-Specific Gene Expression
Figure 8
Model for CHD7-mediated transcriptional modulation in ES cells.
CHD7, via its tandem chromodomains, binds to functional gene enhancers marked with mono- and di-methylated K4 of histone H3. In ES cells a subset of the CHD7 sites are cobound by P300, OCT4, SOX2, and NANOG. Collectively, these proteins coactivate gene expression through enhancer-promoter interactions. A subset of CHD7 sites that are not bound by P300, OCT4, SOX2, and NANOG can also enhance transcription, although the identity of the CHD7-associated factors at these sites is not known (not shown). Reduction of CHD7 levels results in increased transcription of a subset of ES cell-specific genes that are already expressed at reasonably high levels, suggesting an antagonistic role for CHD7 at enhancers. We hypothesize that CHD7 functions similarly at later stages in development, which would imply that dysregulated expression of tissue-specific genes contributes to the pathogenesis of CHARGE syndrome.