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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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The selection and function of cell type-specific enhancers.

Sven Heinz1, Casey E Romanoski2, Christopher Benner1

  • 1Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, San Diego, California 92037, USA.

Nature Reviews. Molecular Cell Biology
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Summary
This summary is machine-generated.

Cell type-specific gene expression relies on enhancers, which are DNA elements regulating gene activity. Super-enhancers, clusters of active enhancers, are crucial for cell identity and function.

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Area of Science:

  • Genomics
  • Molecular Biology
  • Developmental Biology

Background:

  • The human genome encodes hundreds of cell types, each with unique functions.
  • Cell type-specific gene expression is orchestrated by regulatory DNA elements, primarily enhancers.
  • Mammalian genomes possess numerous potential enhancers, but only a subset is active in specific cell types.

Purpose of the Study:

  • To elucidate the mechanisms of cell type-specific enhancer selection.
  • To understand the role of transcription factors in enhancer priming and activation.
  • To investigate the function and genomic organization of super-enhancers.

Main Methods:

  • Analysis of transcription factor binding patterns.
  • Gene expression profiling across different cell types.
  • Investigation of higher-order genomic structures associated with active enhancers.

Main Results:

  • Lineage-determining transcription factors prime enhancers for cell type-specific activity.
  • Signal-dependent transcription factors bind to primed enhancers to regulate gene expression.
  • Super-enhancers, dense clusters of active enhancers, are linked to genes specifying cell identity and function.
  • Enhancer and super-enhancer functions are intertwined with higher-order genomic organization.

Conclusions:

  • Enhancers and super-enhancers are critical regulatory elements for establishing and maintaining cell identity.
  • A coordinated mechanism involving transcription factor binding and genomic organization governs cell type-specific gene expression.