E2f6 and Bmi1 cooperate in axial skeletal development.
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.
Courel
Maria
M
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Friesenhahn
Laurie
L
Lees
Jacqueline A
JA
D000818:Animals; D001842:Bone and Bones / Q000002:abnormalities / Q000033:anatomy & histology / Q000502:physiology*; D002453:Cell Cycle / Q000502:physiology; D002478:Cells, Cultured; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism; D050701:E2F6 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D063150:Polycomb Repressive Complex 1; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012863:Skeleton; D015996:Survival Rate
C489421:Bmi1 protein, mouse; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050701:E2F6 Transcription Factor; C111236:E2f6 protein, mouse; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D063150:Polycomb Repressive Complex 1