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| Subject Categories: Development | Immunology |
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| The EMBO Journal
(2005) 24, 1863–1873, doi:10.1038/sj.emboj.7600654 Published online 5 May 2005 |
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| Impaired maturation of myeloid progenitors in mice lacking novel Polycomb group protein MBT-1 |
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| Satoko Arai and Toru Miyazaki |
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Center for Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA To whom correspondence should be addressed Toru Miyazaki, Center for Immunology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard NA7200, Dallas, TX 75390-9093, USA. Tel.: +1 214 648 7322; Fax: +1 214 648 7331; E-mail: Toru.Miyazaki@UTSouthwestern.edu Received 23 November 2004; Accepted 31 March 2005; Published online 5 May 2005. |
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| Abstract |
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| Polycomb group (PcG) proteins participate in DNA-binding complexes with gene-repressing activity, many of which have been highlighted for their involvement in hematopoiesis. We have identified a putative PcG protein, termed MBT-1, that is associated with Rnf2, an in vivo interactor of PcG proteins. MBT-1 structurally resembles the H-L(3)MBT protein, whose deletion is predicted to be responsible for myeloid hematopoietic malignancies. The human MBT-1 gene is located on chromosome 6q23, a region frequently deleted in leukemia cells, and shows a transient expression spike in response to maturation-inducing stimuli in myeloid leukemia cells. MBT-1-/- myeloid progenitor cells exhibit a maturational deficiency but maintain normal proliferative activities. This results in the accumulation of immature myeloid progenitors and hence, a marked decrease of mature myeloid blood cells, causing the MBT-1-/- mice to die of anemia during a late embryonic stage. Together, we conclude that MBT-1 specifically regulates the maturational advancement of myeloid progenitor cells during transitions between two developmental stages. We also show that MBT-1 appears to influence myelopoiesis by transiently enhancing p57KIP2 expression levels. |
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| Keywords: cyclin-dependent kinase inhibitor (CDKI), hematopoiesis, mbt repeat, polycomb, Rnf2 |
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