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 (TFs), 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 multilayered 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 TFs to targets located in co‐aligned active and inactive nuclear compartments (ANC and INC). It is based on evidence that active, easily accessible chromatin (perichromatin region, PR) lines a network of channels (interchromatin compartment, IC) involved in nuclear import–export functions. The IC and PR constitute the ANC, whereas transcriptionally noncompetent chromatin with higher compactness is part of the likely less accessible 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.

The three‐dimensional cancer nucleus

“…Fluorescent in situ hybridizations (FISHs) on preserved 3D nuclei have enabled a clear understanding of where chromosomes are located in the 3D nuclear space. Seminal work over the years has shown that chromosomes are arranged in a nonrandom and probabilistic manner in the nuclear space of normal cells (Figure ) and that this organization is maintained during evolution . The functional relevance of this ordered structure was elucidated by Solovei et al in a pivotal study on retinas of diurnal and nocturnal animals: in nocturnal animals, the so‐called “inverted” nuclear chromosomal organization is suited to bundle the light—similar to a prism—and enables enhanced vision in dim light conditions.…”

“…The lecture of Boveri's publications is fascinating and is highly recommended to anyone interested in cell biology, genetics, and cancer. in the nuclear space of normal cells [12][13][14] (Figure 3) and that this organization is maintained during evolution. 15 The functional relevance of this ordered structure was elucidated by Solovei et al 16 in a pivotal study on retinas of diurnal and nocturnal animals: in nocturnal animals, the so-called "inverted" nuclear chromosomal organization is suited to bundle the light-similar to a prism-and enables enhanced vision in dim light conditions.…”

“…Chromosome conformation capture technologies have added information on gene and chromosome contacts to FISH studies and are a relevant tool in conjunction with FISH. 13,[17][18][19] A drawback of these technologies is that they average data from many (thousands of ) cells and do not reliably identify contacts in single cells, which FISH is able to do using manual, semi-automated and automated procedures. 20,21 In cancer cells, the nuclear organization of chromosomes and genes is altered.…”

Visualization and sequencing of accessible chromatin reveals cell cycle and post romidepsin treatment dynamics

“…In the human genome, genes fluctuate between various transcriptional states: active, inactive or poised (1)(2)(3). The transcriptional status of each gene is dependent on it's local chromatin architecture and nucleosomal positioning inside the nucleus.…”

Introduction to the special issue “3D nuclear architecture of the genome”

“…Cremer and Cremer focus on the concepts and preliminary experimental evidence for positional changes of transcription regulatory elements within a dynamic, functional nuclear architecture. They propose a multilayered shell‐like chromatin organization of domain clusters where compaction levels are associated with transcriptional accessibility.…”