Dataset Information

Regulation of nuclear NF-?B oscillation by a diffusion coefficient and its biological implications.

ABSTRACT: The transcription factor NF-?B shuttles between the cytoplasm and the nucleus, and nuclear NF-?B is known to oscillate with a cycle of 1.5-2.5 h following the application of external stimuli. Oscillation pattern of NF-?B is implicated in regulation of the gene expression profile. In a previous report, we found that the oscillation pattern of nuclear NF-?B in a computational 3D spherical cell was regulated by spatial parameters such as nuclear to cytoplasmic volume ratio, nuclear transport, locus of protein synthesis, and diffusion coefficient. Here we report analyses and a biological implication for the regulation of oscillation pattern by diffusion coefficient. Our analyses show that the "reset" of nuclear NF-?B, defined as the return of nuclear NF-?B to the initial level or lower, was crucial for the oscillation; this was confirmed by the flux analysis. In addition, we found that the distant cytoplasmic location from the nucleus acted as a "reservoir" for storing newly synthesized I?B?. When the diffusion coefficient of proteins was large (? 10-11 m2/s), a larger amount of I?B? was stored in the "reservoir" with a large flux by diffusion. Subsequently, stored I?B? diffused back to the nucleus, where nuclear NF-?B was "reset" to the initial state. This initiated the next oscillation cycle. When the diffusion coefficient was small (? 10-13 m2/s), oscillation of nuclear NF-?B was not observed because a smaller amount of I?B? was stored in the "reservoir" and there was incomplete "reset" of nuclear NF-?B. If the diffusion coefficient for I?B? was increased to 10-11 m2/s keeping other proteins at 10-13 m2/s, the oscillation was rescued confirming the "reset" and "reservoir" hypothesis. Finally, we showed altered effective value of diffusion coefficient by diffusion obstacles. Thus, organelle crowding seen in stressed cells possibly changes the oscillation pattern by controlling the effective diffusion coefficient.

SUBMITTER: Ohshima D

PROVIDER: S-EPMC4193834 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Regulation of nuclear NF-κB oscillation by a diffusion coefficient and its biological implications.

Ohshima Daisuke D Ichikawa Kazuhisa K

PloS one 20141010 10

The transcription factor NF-κB shuttles between the cytoplasm and the nucleus, and nuclear NF-κB is known to oscillate with a cycle of 1.5-2.5 h following the application of external stimuli. Oscillation pattern of NF-κB is implicated in regulation of the gene expression profile. In a previous report, we found that the oscillation pattern of nuclear NF-κB in a computational 3D spherical cell was regulated by spatial parameters such as nuclear to cytoplasmic volume ratio, nuclear transport, locus ...[more]

PMID: 25302804

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Project description:BackgroundCircadian rhythms comprise oscillating molecular interactions, the disruption of the homeostasis of which would cause various disorders. To understand this phenomenon systematically, an accurate technique to identify oscillating molecules among omics datasets must be developed; however, this is still impeded by many difficulties, such as experimental noise and attenuated amplitude.ResultsTo address these issues, we developed a new algorithm named Maximal Information Coefficient-based Oscillation Prediction (MICOP), a sine curve-matching method. The performance of MICOP in labeling oscillation or non-oscillation was compared with four reported methods using Mathews correlation coefficient (MCC) values. The numerical experiments were performed with time-series data with (1) mimicking of molecular oscillation decay, (2) high noise and low sampling frequency and (3) one-cycle data. The first experiment revealed that MICOP could accurately identify the rhythmicity of decaying molecular oscillation (MCC?>?0.7). The second experiment revealed that MICOP was robust against high-level noise (MCC?>?0.8) even upon the use of low-sampling-frequency data. The third experiment revealed that MICOP could accurately identify the rhythmicity of noisy one-cycle data (MCC?>?0.8). As an application, we utilized MICOP to analyze time-series proteome data of mouse liver. MICOP identified that novel oscillating candidates numbered 14 and 30 for C57BL/6 and C57BL/6 J, respectively.ConclusionsIn this paper, we presented MICOP, which is an MIC-based algorithm, for predicting periodic patterns in large-scale time-resolved protein expression profiles. The performance test using artificially generated simulation data revealed that the performance of MICOP for decaying data was superior to that of the existing widely used methods. It can reveal novel findings from time-series data and may contribute to biologically significant results. This study suggests that MICOP is an ideal approach for detecting and characterizing oscillations in time-resolved omics data sets.

Dataset Information

Regulation of nuclear NF-?B oscillation by a diffusion coefficient and its biological implications.

Publications

Regulation of nuclear NF-κB oscillation by a diffusion coefficient and its biological implications.

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