Abstract
The family of core-binding factors includes the DNA-binding subunits Runx1-3 and their common non-DNA-binding partner CBFβ. We examined the collective role of core-binding factors in hematopoiesis with a hypomorphic Cbfb allelic series. Reducing CBFβ levels by 3- or 6-fold caused abnormalities in bone development, megakaryocytes, granulocytes, and T cells. T-cell development was very sensitive to an incremental reduction of CBFβ levels: mature thymocytes were decreased in number upon a 3-fold reduction in CBFβ levels, and were virtually absent when CBFβ levels were 6-fold lower. Partially penetrant consecutive differentiation blocks were found among early T-lineage progenitors within the CD4-CD8- double-negative 1 and downstream double-negative 2 thymocyte subsets. Our data define a critical CBFβ threshold for normal T-cell development, and situate an essential role for core-binding factors during the earliest stages of T-cell development.
Original language | English |
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Pages (from-to) | 11-21 |
Number of pages | 11 |
Journal | Blood |
Volume | 109 |
Issue number | 1 |
DOIs | |
Publication status | Published - Jan 1 2007 |
All Science Journal Classification (ASJC) codes
- Biochemistry
- Immunology
- Hematology
- Cell Biology