E2f6 and Bmi1 cooperate in axial skeletal development

Dev Dyn. 2008 May;237(5):1232-42. doi: 10.1002/dvdy.21516.

Abstract

Bmi1 is a Polycomb Group protein that functions as a component of Polycomb Repressive Complex 1 (PRC1) to control axial skeleton development through Hox gene repression. Bmi1 also represses transcription of the Ink4a-Arf locus and is consequently required to maintain the proliferative and self-renewal properties of hematopoietic and neural stem cells. Previously, one E2F family member, E2F6, has been shown to interact with Bmi1 and other known PRC1 components. However, the biological relevance of this interaction is unknown. In this study, we use mouse models to investigate the interplay between E2F6 and Bmi1. This analysis shows that E2f6 and Bmi1 cooperate in the regulation of Hox genes, and consequently axial skeleton development, but not in the repression of the Ink4a-Arf locus. These findings underscore the significance of the E2F6-Bmi1 interaction in vivo and suggest that the Hox and Ink4a-Arf loci are regulated by somewhat different mechanisms.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bone and Bones / abnormalities
  • Bone and Bones / anatomy & histology
  • Bone and Bones / physiology*
  • Cell Cycle / physiology
  • Cells, Cultured
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • E2F6 Transcription Factor / genetics
  • E2F6 Transcription Factor / metabolism*
  • Fibroblasts / cytology
  • Fibroblasts / physiology
  • Gene Expression Regulation, Developmental
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Polycomb Repressive Complex 1
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Skeleton*
  • Survival Rate

Substances

  • Bmi1 protein, mouse
  • Cyclin-Dependent Kinase Inhibitor p16
  • E2F6 Transcription Factor
  • E2f6 protein, mouse
  • Homeodomain Proteins
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • Polycomb Repressive Complex 1