Pias3-dependent SUMOylation directs rod photoreceptor development

Neuron. 2009 Jan 29;61(2):234-46. doi: 10.1016/j.neuron.2008.12.006.


Specification of retinal rod photoreceptors is determined by several different transcription factors that activate expression of rod-specific genes and repress expression of cone photoreceptor-specific genes. The mechanism by which this dual regulation occurs is unclear. We have found that Pias3, a transcriptional coregulator and E3 SUMO ligase that is selectively expressed in developing photoreceptors, promotes the differentiation of rod photoreceptors while preventing rods from adopting cone photoreceptor-like characteristics. Pias3 binds the photoreceptor-specific transcription factors Crx and Nr2e3 and is specifically targeted to the promoters of photoreceptor-specific genes. Pias3 SUMOylates Nr2e3, converting it into a potent repressor of cone-specific gene expression. Rod- and cone-specific promoters are bound by hyperSUMOylated proteins in rod photoreceptors, and blocking SUMOylation in photoreceptors results in cells with morphological and molecular features of cones and an absence of rod-specific markers. Our data thus identify Pias3-mediated SUMOylation of photoreceptor-specific transcription factors as a key mechanism of rod specification.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / physiology*
  • Cell Lineage / physiology
  • Gene Expression Regulation, Developmental / genetics
  • Homeodomain Proteins / metabolism
  • Mice
  • Mice, Knockout
  • Neurogenesis / physiology*
  • Orphan Nuclear Receptors
  • Promoter Regions, Genetic / genetics
  • Protein Binding / genetics
  • Protein Inhibitors of Activated STAT / metabolism*
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Retina / cytology
  • Retina / embryology*
  • Retina / metabolism*
  • Retinal Rod Photoreceptor Cells / cytology
  • Retinal Rod Photoreceptor Cells / metabolism*
  • SUMO-1 Protein / metabolism*
  • Trans-Activators / metabolism
  • Transcriptional Activation / physiology


  • Homeodomain Proteins
  • Nr2e3 protein, mouse
  • Orphan Nuclear Receptors
  • Pias3 protein, mouse
  • Protein Inhibitors of Activated STAT
  • Receptors, Cytoplasmic and Nuclear
  • SUMO-1 Protein
  • Trans-Activators
  • cone rod homeobox protein