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The proteomic landscape of the suprachiasmatic nucleus clock reveals large-scale coordination of key biological processes.

PLoS genetics | 2014

The suprachiasmatic nucleus (SCN) acts as the central clock to coordinate circadian oscillations in mammalian behavior, physiology and gene expression. Despite our knowledge of the circadian transcriptome of the SCN, how it impacts genome-wide protein expression is not well understood. Here, we interrogated the murine SCN proteome across the circadian cycle using SILAC-based quantitative mass spectrometry. Of the 2112 proteins that were accurately quantified, 20% (421 proteins) displayed a time-of-day-dependent expression profile. Within this time-of-day proteome, 11% (48 proteins) were further defined as circadian based on a sinusoidal expression pattern with a ∼24 h period. Nine circadianly expressed proteins exhibited 24 h rhythms at the transcript level, with an average time lag that exceeded 8 h. A substantial proportion of the time-of-day proteome exhibited abrupt fluctuations at the anticipated light-to-dark and dark-to-light transitions, and was enriched for proteins involved in several key biological pathways, most notably, mitochondrial oxidative phosphorylation. Additionally, predicted targets of miR-133ab were enriched in specific hierarchical clusters and were inversely correlated with miR133ab expression in the SCN. These insights into the proteomic landscape of the SCN will facilitate a more integrative understanding of cellular control within the SCN clock.

Pubmed ID: 25330117 RIS Download

Associated grants

  • Agency: Canadian Institutes of Health Research, Canada
    Id: MOP 126090
  • Agency: Canadian Institutes of Health Research, Canada
    Id: MOP 86549

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DAVID (tool)

RRID:SCR_001881

Bioinformatics resource system including web server and web service for functional annotation and enrichment analyses of gene lists. Consists of comprehensive knowledgebase and set of functional analysis tools. Includes gene centered database integrating heterogeneous gene annotation resources to facilitate high throughput gene functional analysis.

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Bioinformatic Harvester IV (beta) at Karlsruhe Institute of Technology (tool)

RRID:SCR_008017

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Program to Reduce Incontinence by Diet and Exercise (tool)

RRID:SCR_009018

Randomized controlled trial being conducted at two clinical centers in the United States to learn more about the effects of weight loss on urinary incontinence. About 330 overweight women aged 30 or older will participate and will be followed for 18 months. Efficacy of weight reduction as a treatment for urinary incontinence will be examined at 6 months following the intensive weight control program, and the sustained impact of the intervention will be examined at 18 months. To increase the maintenance of weight reduction and facilitate evaluation of the enduring impact of weight loss on urinary incontinence, they propose to study a motivation-based weight maintenance program. At the end of the intensive weight control program, women randomized to the weight loss program will be randomized to either a 12-month skill-based maintenance intervention or to a motivation-based maintenance intervention. The maintenance interventions maximize the potential for sustained weight loss and will allow them to determine if long-term weight reduction will produce continued improvement in urinary incontinence.

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Canadian Institutes of Health Research (tool)

RRID:SCR_012838

The Canadian Institutes of Health Research (CIHR) is the Government of Canada''s agency responsible for funding health research in Canada. CIHR was created in 2000 under the authority of the CIHR Act and reports to Parliament through the Minister of Health. CIHR''s budget for 2008-09 is $928.6 million, of which $132 million is allocated to administering the Networks of Centres of Excellence and Canada Research Chair programs. CIHR was created to transform health research in Canada by: * funding more research on targeted priority areas; * building research capacity in under-developed areas such as population health and health services research; * training the next generation of health researchers; and * focusing on knowledge translation, so that the results of research are transformed into policies, practices, procedures, products and services. CIHR consists of 13 virtual institutes, a structure that is unique in the world. These innovative institutes bring together all partners in the research process - the people who fund research, those who carry it out and those who use its results - to share ideas and focus on what Canadians need: good health and the means to prevent disease and fight it when it happens. Each institute supports a broad spectrum of research in its topic areas and, in consultation with its stakeholders, sets priorities for research in those areas.

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MaxQuant (tool)

RRID:SCR_014485

A quantitative proteomics software package for analyzing large-scale mass-spectrometric data sets. It is a set of algorithms that include peak detection and scoring of peptides, mass calibration, database searches for protein identification, protein quantification, and provides summary statistics.

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Neuro-2a (tool)

RRID:CVCL_0470

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C57BL/6J (tool)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

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