The use of imaging techniques has become an essential tool in cell biology. In particular, advances in fluorescence microscopy and conventional transmission electron microscopy have had a major impact on our understanding of chromatin structure and function. In this review we attempt to chart the conceptual evolution of models describing the organization and function of chromatin in higher eukaryotic cells, in parallel with the advances in light and electron microscopy over the past 50 years. In the last decade alone, the application of energy filtered transmission electron microscopy (EFTEM), also referred to as electron spectroscopic imaging (ESI), has provided many new insights into the organization of chromatin in the interphase nucleus. Based on ESI imaging of chromatin in situ, we propose a ‘lattice’ modelfor the organization of chromatin in interphase cells. In this model, the chromatin fibers of 10 and 30 nm diameter observed by ESI, produce a meshwork that accommodates an extensive and distributed interchromosomal (IC) space devoid of chromatin. The functional implications of this model for nuclear activity are discussed.

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