Cited by 47Hematopoietic Stem Cell TransplantationGenomics and Chromatin DynamicsAcute Myeloid Leukemia Research

Adult Hematopoiesis is Regulated by TIF1γ, 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·2011·Cell stem cell

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.

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Crossref · 10.1016/j.stem.2011.02.005

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Authors
Kusy, S., Gault, N., Ferri, F., Lewandowski, D., Barroca, V., Jaracz-Ros, A., Losson, R., & Romeo, P.-H.
Affiliations
  • Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR)
  • Université Paris-Sud (FR)
Venue
Cell stem cell
Publisher
Elsevier BV
Published
2011-04
Volume
8
Issue
4
Pages
412-425
ISSN
  • 1875-9777 (ISSN-L)
  • 1934-5909
OpenAlex
W1988109049
Cited by
47
References
43
Citations by year
2025: 1 · 2024: 4 · 2022: 1 · 2021: 1 · 2020: 3 · 2019: 8 · 2018: 1 · 2017: 4 · 2016: 4 · 2015: 3 · 2014: 4 · 2013: 3 · 2012: 5
FWCI
3.72
Type
journal article
Language
en
Open access
Locations
  • Cell stem cell (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
Topics
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
Keywords
TIF1γ, adult hematopoiesis, TAL1, PU.1, transcriptional repression, hematopoietic stem cells, TGF-beta signaling, cell-autonomous regulation
MeSH terms
T-Cell Acute Lymphocytic Leukemia Protein 1, Proto-Oncogene Protein Spi-1, Hematopoiesis, Proto-Oncogene Proteins, Repressor Proteins, Transcription Factors, Transcription, Genetic, Trans-Activators, Down-Regulation, Basic Helix-Loop-Helix Proteins

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