Abstract
The Polycomb group (PcG) gene Bmi1 promotes cell proliferation and stem cell self-renewal by repressing the Ink4a/Arf locus. We used a genetic approach to investigate whether Ink4a or Arf is more critical for relaying Bmi1 function in lymphoid cells, neural progenitors, and neural stem cells. We show that Arf is a general target of Bmi1, however particularly in neural stem cells, derepression of Ink4a contributes to Bmi1(-/-) phenotypes. Additionally, we demonstrate haploinsufficient effects for the Ink4a/Arf locus downstream of Bmi1 in vivo. This suggests differential, cell type-specific roles for Ink4a versus Arf in PcG-mediated (stem) cell cycle control.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Differentiation
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Cell Proliferation
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Cellular Senescence
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Cerebellum / cytology
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Cyclin-Dependent Kinase Inhibitor p16 / deficiency
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Cyclin-Dependent Kinase Inhibitor p16 / metabolism
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Genes, p16*
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Heterozygote
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Lymphoid Tissue / cytology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Multipotent Stem Cells / cytology*
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Multipotent Stem Cells / metabolism*
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Neurons / cytology*
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Neurons / metabolism*
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Nuclear Proteins / deficiency*
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Nuclear Proteins / genetics
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Polycomb Repressive Complex 1
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Proto-Oncogene Proteins / deficiency*
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Proto-Oncogene Proteins / genetics
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Repressor Proteins / genetics
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Repressor Proteins / metabolism
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Tumor Suppressor Protein p14ARF / deficiency
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Tumor Suppressor Protein p14ARF / genetics*
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Tumor Suppressor Protein p14ARF / metabolism
Substances
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Bmi1 protein, mouse
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Cdkn2a protein, mouse
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Cyclin-Dependent Kinase Inhibitor p16
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Nuclear Proteins
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Proto-Oncogene Proteins
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RNA, Messenger
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Repressor Proteins
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Tumor Suppressor Protein p14ARF
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Polycomb Repressive Complex 1