Adult Hematopoiesis is Regulated by TIF1γ, a Repressor of TAL1 and PU.1 Transcriptional Activity

• DOI: 10.1016/j.stem.2011.02.005
• Publication Date: 2011-04-09T06:07:54Z
• Authors: Sophie Kusy; Nathalie Gault; Federica Ferri; Daniel Lewandowski; Vilma Barroca; Agnieszka Jaracz-Ros; Regine Losson; Paul-Henri Romeo
• Keywords: 0301 basic medicine; Transcription, Genetic; Down-Regulation; Cell Biology; Hematopoiesis; Repressor Proteins; 03 medical and health sciences; Proto-Oncogene Proteins; Genetics; Basic Helix-Loop-Helix Transcription Factors; Trans-Activators; Molecular Medicine; T-Cell Acute Lymphocytic Leukemia Protein 1; Transcription Factors

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.