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Myeloid translocation gene 16 is required for maintenance of haematopoietic stem cell quiescence.
- Source :
-
The EMBO journal [EMBO J] 2012 Mar 21; Vol. 31 (6), pp. 1494-505. Date of Electronic Publication: 2012 Jan 20. - Publication Year :
- 2012
-
Abstract
- The t(8;21) and t(16;21) that are associated with acute myeloid leukaemia disrupt two closely related genes termed Myeloid Translocation Genes 8 (MTG8) and 16 (MTG16), respectively. Many of the transcription factors that recruit Mtg16 regulate haematopoietic stem and progenitor cell functions and are required to maintain stem cell self-renewal potential. Accordingly, we found that Mtg16-null bone marrow (BM) failed in BM transplant assays. Moreover, when removed from the animal, Mtg16-deficient stem cells continued to show defects in stem cell self-renewal assays, suggesting a requirement for Mtg16 in this process. Gene expression analysis indicated that Mtg16 was required to suppress the expression of several key cell-cycle regulators including E2F2, and chromatin immunoprecipitation assays detected Mtg16 near an E2A binding site within the first intron of E2F2. BrdU incorporation assays indicated that in the absence of Mtg16 more long-term stem cells were in the S phase, even after competitive BM transplantation where normal stem and progenitor cells are present, suggesting that Mtg16 plays a role in the maintenance of stem cell quiescence.
- Subjects :
- Animals
Basic Helix-Loop-Helix Transcription Factors genetics
Basic Helix-Loop-Helix Transcription Factors metabolism
Binding Sites
Cells, Cultured
E2F2 Transcription Factor genetics
E2F2 Transcription Factor metabolism
Gene Expression
Hematopoietic Stem Cells cytology
Hematopoietic Stem Cells metabolism
Leukemia, Myeloid, Acute genetics
Leukemia, Myeloid, Acute metabolism
Leukemia, Myeloid, Acute pathology
Mice
Mice, Inbred C57BL
Mice, Nude
Repressor Proteins
S Phase genetics
Hematopoietic Stem Cells physiology
Nuclear Proteins genetics
Nuclear Proteins metabolism
Transcription Factors genetics
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2075
- Volume :
- 31
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- The EMBO journal
- Publication Type :
- Academic Journal
- Accession number :
- 22266796
- Full Text :
- https://doi.org/10.1038/emboj.2011.500