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Higher order arrangement of the eukaryotic nuclear bodies.

ABSTRACT: The nuclei of eukaryotic cells consist of discrete substructures. These substructures include the nuclear bodies, which have been implicated in a number of biological processes such as transcription and splicing. However, for most nuclear bodies, the details of involvement in these processes in relation to their three-dimensional distributions in the nucleus are still unclear. Through the analysis of TDP, a protein functional in both transcriptional repression and alternative splicing, we have identified a new category of nuclear bodies within which the TDP molecules reside. Remarkably, the TDP bodies (TBs) colocalize or overlap with several different types of nuclear bodies previously suggested to function in transcription or splicing. Of these nuclear bodies, the Gemini of coiled bodies (GEM) seems to associate with TB through the interaction between survival motor neuron (SMN) protein and TDP. Furthermore, TB sometimes appears to be the bridge of two or more of these other nuclear bodies. Our data suggest the existence of a hierarchy and possibly functional arrangement of the nuclear bodies within the eukaryotic nuclei.

SUBMITTER: Wang IF

PROVIDER: S-EPMC129717 | biostudies-literature | 2002 Oct

REPOSITORIES: biostudies-literature

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Publications

Higher order arrangement of the eukaryotic nuclear bodies.

Wang I-Fan IF Reddy Narsa M NM Shen C-K James CK

Proceedings of the National Academy of Sciences of the United States of America 20021002 21

The nuclei of eukaryotic cells consist of discrete substructures. These substructures include the nuclear bodies, which have been implicated in a number of biological processes such as transcription and splicing. However, for most nuclear bodies, the details of involvement in these processes in relation to their three-dimensional distributions in the nucleus are still unclear. Through the analysis of TDP, a protein functional in both transcriptional repression and alternative splicing, we have i ...[more]

PMID: 12361981

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Project description:It is increasingly being recognized that physical interactions between distant chromosomal loci influence the expressivity of the genome. Thus, multiple enhancers may converge on a single gene promoter 1,2 and a single enhancer can stochastically loop to multiple promoters 3. Regulatory elements from neighboring domains or from other chromosomes may interact to generate chromatin structures poised for transcription4-8 or repression 9-11. However, a broader perspective on the formation and function of such networks remains largely unexplored. Using the high-resolution 4C (Circular Chromosome Conformation Capture) analysis, we identify here a genome-wide physical network between genomically imprinted domains impinging H19 imprinting control region (ICR). Sequences interacting with the H19 ICR constitutively map at or within most of known imprinted domains both in mouse embryonic stem cells and in vitro-derived embryoid bodies, despite distinct differences in chromatin environments. Moreover, all-to-all 3D DNA FISH analyses revealed that imprinted domains from 7 different chromosomes co-localize with each other in pair-wise patterns, highlighting the dynamic nature of these interactions. The observed interaction network is dependent on CTCF binding sites within the maternally inherited H19 ICR allele and delays reprogramming of epigenetic features at imprinted domains during male germline development. As other imprinted regions can interact with each other in an H19 ICR-dependent manner, the H19 ICR emerges as an organizer of chromosomal networks by specifically recognizing and reconfiguring imprinted domains. We propose that an ancient key regulatory region, such as the H19 ICR, gradually impacted epigenetic modifications via long-range interactions in the germline to facilitate the recruitment of imprinted genes and their formation in clusters during mammalian radiation. Furthermore, the perspective of epigenetic lesions de-stabilizing such chromosomal networks may advance our understanding of how quantitative traits influence human diseases, such as cancer.

Dataset Information

Higher order arrangement of the eukaryotic nuclear bodies.

Publications

Higher order arrangement of the eukaryotic nuclear bodies.

Similar Datasets

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