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Related Concept Videos

General Transcription Factors01:30

General Transcription Factors

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Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
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Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
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Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
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Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
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Regulation of Expression at Multiple Steps01:23

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The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
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Tissue-specific regulatory circuits reveal variable modular perturbations across complex diseases.

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Summary

Scientists mapped human gene regulatory networks to understand complex diseases. This resource links genetic variants to cell-specific regulatory modules, aiding disease research.

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Area of Science:

  • Genomics
  • Systems Biology
  • Molecular Biology

Background:

  • Understanding the molecular basis of complex diseases is challenging.
  • Gene regulatory networks (GRNs) are crucial for cellular function and disease.
  • Identifying cell-type-specific GRNs is essential for disease mechanism elucidation.

Purpose of the Study:

  • To develop a comprehensive resource of human cell type- and tissue-specific gene regulatory networks.
  • To investigate the role of genetic variants in perturbing these networks in the context of complex diseases.
  • To provide a platform for systematic analysis of regulatory programs across diverse human cell types and tissues.

Main Methods:

  • Construction of 394 human cell type- and tissue-specific gene regulatory networks.
  • Genome-wide connectivity mapping of transcription factors, enhancers, promoters, and genes.
  • Integration of GRN data with 37 genome-wide association studies (GWASs).

Main Results:

  • The developed resource provides genome-wide connectivity information for human GRNs.
  • Disease-associated genetic variants, including sub-threshold ones, were found to perturb cell-type-specific regulatory modules.
  • These perturbations were highly specific to disease-relevant cell types or tissues.

Conclusions:

  • The comprehensive GRN resource enables systematic analysis of regulatory programs in human health and disease.
  • This resource facilitates the identification of disease mechanisms driven by genetic variants acting on specific regulatory modules.
  • The findings highlight the importance of cell-type specificity in understanding the genetic architecture of complex diseases.