Syracuse

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

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Kusy, Sophie | Gault, Nathalie | Ferri, Federica | Lewandowski, Daniel | Barroca, Vilma | Jaracz-Ros, Agnieszka | Losson, Regine | Romeo, Paul-Henri

Edité par CCSD ; Cambridge, MA : Cell Press -

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.

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