| First Author | Kusy S | Year | 2011 |
| Journal | Cell Stem Cell | Volume | 8 |
| Issue | 4 | Pages | 412-25 |
| PubMed ID | 21474105 | Mgi Jnum | J:171356 |
| Mgi Id | MGI:4949785 | Doi | 10.1016/j.stem.2011.02.005 |
| Citation | Kusy S, et al. (2011) Adult Hematopoiesis is Regulated by TIF1gamma, a Repressor of TAL1 and PU.1 Transcriptional Activity. Cell Stem Cell 8(4):412-25 |
| abstractText | Crosstalk between transcription factors and cytokines precisely regulates tissue homeostasis. Transcriptional intermediary factor 1gamma (TIF1gamma) regulates vertebrate hematopoietic development, can control transcription elongation, and is a component of the TGF-beta signaling pathway. Here we show that deletion of TIF1gamma in adult hematopoiesis is compatible with life and long-term maintenance of essential blood cell lineages. However, loss of TIF1gamma results in deficient long-term hematopoietic stem cell (LT-HSC) transplantation activity, deficient short-term HSC (ST-HSC) bone marrow retention, and priming ST-HSCs to myelomonocytic lineage. These defects are hematopoietic cell-autonomous, and priming of TIF1gamma-deficient ST-HSCs can be partially rescued by wild-type hematopoietic cells. TIF1gamma can form complexes with TAL1 or PU.1-two essential DNA-binding proteins in hematopoiesis-occupy specific subsets of their DNA binding sites in vivo, and repress their transcriptional activity. These results suggest a regulation of adult hematopoiesis through TIF1gamma-mediated transcriptional repression of TAL1 and PU.1 target genes. |
