Fluorescence-based confocal imaging analysis of CHD2 mutations in COS-7 cells. (A) Nuclear distribution of CHD2^wt and CHD2^L1270F. Recombinant CHD2^wt shows a finely granulated homogeneous distribution within the cell nucleus, whereas the CHD2^L1270F mutation induces a remarkably speckled distribution of the protein in large punctated bodies. (B-C) Association of CHD2^wt and CHD2^L1270F with active chromatin. CHD2^wt shows a strong colocalization with the transcriptionally active chromatin markers H4Ac and H3K4me3. Strong functional impact can be predicted from the complete loss of colocalization of the mutant form CHD2^L1270F with the gene-expressing chromatin regions. tM is expressed as mean ± standard deviation. n, number of nuclei analyzed per sample.