Adult Hematopoiesis is Regulated by TIF1γ, a Repressor of TAL1 and PU.1 Transcriptional Activity
Open accessAbstract
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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Knockdown of TRIM33 led to an increase in PU.1 occupancy and H3K27 acetylation at Bim -117, suggesting that TRIM33 antagonizes PU.1 binding to DNA and suppresses enhancer activity.
“Interestingly, knockdown of TRIM33 led to an increase in PU.1 occupancy and H3K27 acetylation at Bim –117, suggesting that TRIM33 antagonizes PU.1 binding to DNA and suppresses enhancer activity”
From The transcriptional cofactor TRIM33 prevents apoptosis in B lymphoblastic leukemia by deactivating a single enhancer (2015) · cites this paper as Kusy et al., 2011
The unusual enhancer selectivity of TRIM33 in B-ALL is traced to the density of PU.1.
“We trace this unusual enhancer selectivity of TRIM33 in B-ALL to the density of PU.1”
From The transcriptional cofactor TRIM33 prevents apoptosis in B lymphoblastic leukemia by deactivating a single enhancer (2015) · cites this paper as Kusy et al., 2011
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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
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 838 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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