Dataset Information

Differential tissue specific, temporal and spatial expression patterns of the Aggrecan gene is modulated by independent enhancer elements.

ABSTRACT: The transcriptional mechanism through which chondrocytes control the spatial and temporal composition of the cartilage tissue has remained largely elusive. The central aim of this study was to identify whether transcriptional enhancers played a role in the organisation of the chondrocytes in cartilaginous tissue. We focused on the Aggrecan gene (Acan) as it is essential for the normal structure and function of cartilage and it is expressed developmentally in different stages of chondrocyte maturation. Using transgenic reporter studies in mice we identified four elements, two of which showed individual chondrocyte developmental stage specificity. In particular, one enhancer (-80) distinguishes itself from the others by being predominantly active in adult cartilage. Furthermore, the -62 element uniquely drove reporter activity in early chondrocytes. The remaining chondrocyte specific enhancers, +28 and -30, showed no preference to chondrocyte type. The transcription factor SOX9 interacted with all the enhancers in vitro and mutation of SOX9 binding sites in one of the enhancers (-30) resulted in a loss of its chondrocyte specificity and ectopic enhancer reporter activity. Thus, the Acan enhancers orchestrate the precise spatiotemporal expression of this gene in cartilage types at different stages of development and adulthood.

SUBMITTER: Li IMH

PROVIDER: S-EPMC5772622 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Differential tissue specific, temporal and spatial expression patterns of the Aggrecan gene is modulated by independent enhancer elements.

Li Ian M H IMH Liu Ke K Neal Alice A Clegg Peter D PD De Val Sarah S Bou-Gharios George G

Scientific reports 20180117 1

The transcriptional mechanism through which chondrocytes control the spatial and temporal composition of the cartilage tissue has remained largely elusive. The central aim of this study was to identify whether transcriptional enhancers played a role in the organisation of the chondrocytes in cartilaginous tissue. We focused on the Aggrecan gene (Acan) as it is essential for the normal structure and function of cartilage and it is expressed developmentally in different stages of chondrocyte matur ...[more]

PMID: 29343853

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Project description:BackgroundThe objective of this study is to analyze the spatial and temporal patterns of malaria incidence as to determine the means by which climatic factors such as temperature, rainfall and humidity affect its distribution in Maputo province, Mozambique.MethodsThis study presents a model of malaria that evolves in space and time in Maputo province-Mozambique, over a ten years period (1999-2008). The model incorporates malaria cases and their relation to environmental variables. Due to incompleteness of climatic data, a multiple imputation technique is employed. Additionally, the whole province is interpolated through a Gaussian process. This method overcomes the misalignment problem of environmental variables (available at meteorological stations--points) and malaria cases (available as aggregates for every district--area). Markov Chain Monte Carlo (MCMC) methods are used to obtain posterior inference and Deviance Information Criteria (DIC) to perform model comparison.ResultsA Bayesian model with interaction terms was found to be the best fitted model. Malaria incidence was associated to humidity and maximum temperature. Malaria risk increased with maximum temperature over 28 °C (relative risk (RR) of 0.0060 and 95% Bayesian credible interval (CI) of 0.00033-0.0095) and humidity (relative risk (RR) of 0.00741 and 95% Bayesian CI 0.005141-0.0093). The results would suggest that additional non-climatic factors including socio-economic status, elevation, etc. also influence malaria transmission in Mozambique.ConclusionsThese results demonstrate the potential of climate predictors particularly, humidity and maximum temperature in explaining malaria incidence risk for the studied period in Maputo province. Smoothed maps obtained as monthly average of malaria incidence allowed to visualize months of initial and peak transmission. They also illustrate a variation on malaria incidence risk that might not be related to climatic factors. However, these factors are still determinant for malaria transmission and intensity in the region.

Dataset Information

Differential tissue specific, temporal and spatial expression patterns of the Aggrecan gene is modulated by independent enhancer elements.

Publications

Differential tissue specific, temporal and spatial expression patterns of the Aggrecan gene is modulated by independent enhancer elements.

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