Nuclear compartmentalization, dynamics and function of regulatory DNA sequences

Abstract

Transcription regulatory elements (TREs) have been extensively studied on the biochemical level with respect to their interactions with transcription factors, other DNA segments and larger protein complexes. In this review we describe concepts and preliminary experimental evidence for positional changes of TREs within a dynamic, functional nuclear architecture. We suggest a multi‐layered shell‐like chromatin organization of chromatin domain clusters with increasing chromatin compaction levels from the periphery toward the interior with a decondensed transcriptionally active peripheral layer and compact repressed chromatin typically located in the interior. This model organization of nuclear architecture implies a differential accessibility of transcription factors to targets located in co‐aligned active and inactive nuclear compartments. It is based on evidence that active, easily accessible chromatin (perichromatin, PR) lines a network of channels (interchromatin compartment, IC) involved in nuclear import‐export functions. The IC and PR constitute the active nuclear compartment (ANC), whereas transcriptionally non‐competent chromatin with higher compactness is part of the likely less accessible inactive nuclear compartment (INC). Preliminary experimental evidence shows an enrichment of active TREs in the ANC and of inactive TREs in the INC suggesting positional changes of TREs between the ANC and INC depending on changes in their functional state.

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