Crosstalk between transcription factors and cytokines precisely regulates tissue homeostasis. Transcriptional intermediary factor 1γ (TIF1γ) regulates vertebrate hematopoietic development, can control transcription elongation, and is a component of the TGF-β signaling pathway. Here we show that deletion of TIF1γ in adult hematopoiesis is compatible with life and long-term maintenance of essential blood cell lineages. However, loss of TIF1γ 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 TIF1γ-deficient ST-HSCs can be partially rescued by wild-type hematopoietic cells. TIF1γ 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 TIF1γ-mediated transcriptional repression of TAL1 and PU.1 target genes. © 2011 Elsevier Inc.
Kusy, S., Gault, N., Ferri, F., Lewandowski, D., Barroca, V., Jaracz-Ros, A., … Romeo, P. H. (2011). Adult hematopoiesis is regulated by TIF1γ, a repressor of TAL1 and PU.1 transcriptional activity. Cell Stem Cell, 8(4), 412–425. https://doi.org/10.1016/j.stem.2011.02.005