Elucidating the role of chromatin-modifying complexes in autism spectrum disorder

  • Awarded: 2019
  • Award Type: Pilot
  • Award #: 609562

Genes encoding chromatin-remodeling enzymes are among the most prominent targets of de novo mutations associated with autism spectrum disorder (ASD). It remains uncertain how chromatin remodelers contribute to neurodevelopment at the mechanistic level and, in turn, how genetic mutations disrupt these functions. Filling this gap in our knowledge might help us to better understand how ASD arises.

Pierre Mattar and colleagues have preliminary findings to suggest that chromatin-remodeling enzymes from the chromodomain helicase (CHD) family form protein complexes with the transcription factor ADNP. Like CHD genes, ADNP is among the most common de novo mutated genes associated with ASD. Since these proteins form complexes in neural progenitor cells, this data suggest that these protein complexes might regulate the function of these cells during development.

Mattar’s team proposes to determine whether and how ASD-linked mutations in ADNP disrupt interactions between CHD and ADNP proteins and to test how these protein complexes regulate neurogenesis in the developing mouse neocortex. They anticipate that the successful completion of this work will identify and characterize a novel molecular pathway that contributes to ASD, helping to shed light on the etiology of this complex disorder.

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