title: Adult hematopoiesis is regulated by TIF1γ, a repressor of TAL1 and PU.1 transcriptional activity.
abstract: 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.
authors.affiliation: Commissariat à l'Energie Atomique, DSV/iRCM/LRTS, 92265 Fontenay-aux-Roses cedex, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Kusy
authors.forename: Nathalie
authors.initials: N
authors.lastname: Gault
authors.forename: Federica
authors.initials: F
authors.lastname: Ferri
authors.forename: Daniel
authors.initials: D
authors.lastname: Lewandowski
authors.forename: Vilma
authors.initials: V
authors.lastname: Barroca
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Jaracz-Ros
authors.forename: Regine
authors.initials: R
authors.lastname: Losson
authors.forename: Paul-Henri
authors.initials: PH
authors.lastname: Romeo
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D006410:Hematopoiesis / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D015534:Trans-Activators; D014157:Transcription Factors; D000099232:Proto-Oncogene Protein Spi-1; C511956:TRIM33 protein, human; C067143:TAL1 protein, human