PIAS1 confers DNA-binding specificity on the Msx1 homeoprotein

Hansol Lee, John C. Quinn, Kannanganattu V. Prasanth, Victoria A. Swiss, Kyriakos D. Economides, Marie M. Camacho, David L. Spector, Cory Abate-Shen

Research output: Contribution to journalArticle

Abstract

The mechanisms by which homeoproteins bind selectively to target genes in vivo have long remained unresolved. Here we report that PIAS1 confers DNA-binding specificity on the Msx1 homeoprotein by regulating its subnuclear localization and proximity to target genes. We demonstrate that the interaction of Msx1 with PIAS1, but not its sumoylation, is required for Msx1 to function as an inhibitor of myoblast differentiation through repression of myogenic regulatory genes, such as MyoD. We find that PIAS1 enables Msx1 to bind selectively to a key regulatory element in MyoD, the CER, in myoblast cells and to distinguish the CER from other nonregulatory TAAT-containing sequences. We show that PIAS1 is required for the appropriate localization and retention of Msx1 at the nuclear periphery in myoblast cells. Furthermore, we demonstrate that myogenic regulatory genes that are repressed by Msx1, namely MyoD and Myf5, are located at the nuclear periphery in myoblast cells. We propose that a key regulatory event for DNA-binding specificity by homeoproteins in vivo is their appropriate targeting to subnuclear compartments where their target genes are located, which can be achieved by cofactors such as PIAS1.

Original languageEnglish (US)
Pages (from-to)784-794
Number of pages11
JournalGenes and Development
Volume20
Issue number7
DOIs
StatePublished - Apr 1 2006

Keywords

  • DNA-binding specificity
  • Homeobox genes
  • Myoblast differentiation
  • PIAS genes
  • Protein-protein interactions
  • Sumoylation

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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    Lee, H., Quinn, J. C., Prasanth, K. V., Swiss, V. A., Economides, K. D., Camacho, M. M., Spector, D. L., & Abate-Shen, C. (2006). PIAS1 confers DNA-binding specificity on the Msx1 homeoprotein. Genes and Development, 20(7), 784-794. https://doi.org/10.1101/gad.1392006