Higher order chromatin architecture in the cell nucleus: on the way from structure to function

The cell nucleus is a highly compartmentalized structure. In this review we describe controversial views on higher order chromatin organization from the level of higher order chromatin domains built up from folded chromatin fibers to the level of chromosome territories and the interchromatin compartment (IC), which harbors non-chromatin nuclear domains, such as interchromatin granule clusters (IGCs visualized in the electron microscope) or splicing factorcontaining speckles (visualized by fluorescence microscopy). Emphasis is laid on the definition and functional importance of a nuclear compartment located at the periphery of chromatin domains in direct contact with the IC, termed the perichromatin region (PR). Ongoing experiments to elucidate the topological relationships between PR and IC have provided new insights into the functional interplay between transcription and splicing. As an example, we discuss the structure and nuclear topology of perichromatin fibrils (FPs) contained in the PR and their functional interplay with IGCs/speckles. In addition we discuss the advantages and drawbacks of experimental approaches currently used to study nuclear architecture and function in fixed and living cells.