Adam13 interacts with large protein complexes to regulate histone modification and gene expression

Ankit Pandey1, Helene Cousin1, Shiv Kumar1,2,3

  • 1Department of Veterinary and Animal Sciences, University of Massachusetts Amherst, Amherst, MA, United States.

Insights

Cranial neural crest (CNC) cell development relies on ADAM proteins, which interact with Arid3a to regulate gene expression and histone modifications. This interaction is crucial for CNC cell migration and facial structure formation.

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Genetics

Background:

  • Cranial neural crest (CNC) cells are vital stem-cell-like tissues for vertebrate facial development.
  • Disintegrin and metalloproteinase (ADAM) proteins are essential for CNC cell induction and migration.

Purpose of the Study:

  • To investigate the interaction between Adam13 and Arid3a in regulating gene expression and histone modifications within CNC cells.
  • To elucidate the role of Adam13 in tfap2α expression and its impact on CNC migration.

Main Methods:

  • Analysis of Adam13-Arid3a interactions.
  • Assessment of histone modifications in CNC cells.
  • Investigation of Arid3a binding to the tfap2α promoter.
  • Examination of gene expression and RNA splicing.

Main Results:

  • Adam13 modulates histone modifications in CNC cells.
  • Arid3a binding to the tfap2α promoter is dependent on Adam13.
  • Adam13 promotes a specific tfap2α variant crucial for CNC migration.
  • Adam13 and ADAM9 associate with proteins involved in histone modification and RNA splicing.

Conclusions:

  • ADAM proteins may function as extracellular sensors influencing chromatin accessibility.
  • This modulation affects gene expression and RNA splicing, critical for CNC development.
  • The Adam13-Arid3a pathway is key to regulating genes essential for CNC migration and facial development.

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