Adult hematopoiesis is regulated by TIF1gamma, a repressor of TAL1 and PU.1 transcriptional activity

Sophie Kusy , Nathalie Gault , Federica Ferri (1, 2) , Daniel Lewandowski , Vilma Barroca , Agnieszka Jaracz-Ros , Regine Losson (3, 2) , Paul-Henri Romeo

1 IRM - Immuno-Rhumatologie Moléculaire
2 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire
3 IGBMC - Institut de génétique et biologie moléculaire et cellulaire

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.

Domaines: Biochimie, Biologie Moléculaire

Sophie Kusy, Nathalie Gault, Federica Ferri, Daniel Lewandowski, Vilma Barroca, et al.. Adult hematopoiesis is regulated by TIF1gamma, a repressor of TAL1 and PU.1 transcriptional activity. Cell stem cell, 2011, 8 (4), pp.412-425. ⟨10.1016/j.stem.2011.02.005⟩. ⟨hal-04306407⟩