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One day in 2006, while a postdoc in the Rockefeller University laboratory of Nathaniel Heintz, I had an unexpected eye-opener. Heintz showed me some electron microscopy images of Purkinje neuron nuclei in the murine cerebellum. They stunned me—the heterochromatin localization in the nucleus was different from anything I’d ever seen before. Rather than the dispersed, irregular patches with enrichment near the nuclear membrane typical of many cells, nearly all the heterochromatin was in the center of the nucleus, adhered to the single large nucleolus. Not only did heterochromatin organization look different, the volume of it in Purkinje neurons seemed much lower, too. Because links between DNA methylation and heterochromatin proteins were suggested in the literature, we thought that DNA methylation might be depleted in Purkinje ...
