TAF1,the largest subunit of TFIID, is dispensable for adult hematopoiesis [Pro-seq]
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ABSTRACT:
PROVIDER: PRJNA1045527 | ENA |
REPOSITORIES: ENA
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Project description:While many sequence-specific transcription factors (TFs) have been identified as key regulators of hematopoietic stem cell (HSC) lineage determination, the function of general TFs in HSC behavior is poorly understood. To evaluate the function of the TFIID subunit TAF1 in normal hematopoiesis, we generated Taf1 conditional knockout mice and identified an essential role of TAF1 in fetal erythropoiesis. Surprisingly, TAF1 deletion in adult mice was not lethal to hematopoiesis; rather, we observed a marked expansion of the hematopoietic stem and progenitor cell (HSPC) compartment, with increased self-renewal and impaired differentiation capacity in these cells. TAF1-null HSPCs failed to produce mature blood cells in chimeric mice; these cells also failed to up-regulate key differentiation genes when induced to differentiate in vitro. TAF1 loss not only disrupted TFIID assembly and chromatin recruitment, but also reduced RNAPII promoter-proximal pausing. Thus, HSPCs utilize distinct transcriptional regulatory mechanisms to undergo differentiation versus maintaining self-renewal.
2025-07-09 | GSE248649 | GEO
Project description:While many sequence-specific transcription factors (TFs) have been identified as key regulators of hematopoietic stem cell (HSC) lineage determination, the function of general TFs in HSC behavior is poorly understood. To evaluate the function of the TFIID subunit TAF1 in normal hematopoiesis, we generated Taf1 conditional knockout mice and identified an essential role of TAF1 in fetal erythropoiesis. Surprisingly, TAF1 deletion in adult mice was not lethal to hematopoiesis; rather, we observed a marked expansion of the hematopoietic stem and progenitor cell (HSPC) compartment, with increased self-renewal and impaired differentiation capacity in these cells. TAF1-null HSPCs failed to produce mature blood cells in chimeric mice; these cells also failed to up-regulate key differentiation genes when induced to differentiate in vitro. TAF1 loss not only disrupted TFIID assembly and chromatin recruitment, but also reduced RNAPII promoter-proximal pausing. Thus, HSPCs utilize distinct transcriptional regulatory mechanisms to undergo differentiation versus maintaining self-renewal.
2025-07-09 | GSE248648 | GEO
Project description:While many sequence-specific transcription factors (TFs) have been identified as key regulators of hematopoietic stem cell (HSC) lineage determination, the function of general TFs in HSC behavior is poorly understood. To evaluate the function of the TFIID subunit TAF1 in normal hematopoiesis, we generated Taf1 conditional knockout mice and identified an essential role of TAF1 in fetal erythropoiesis. Surprisingly, TAF1 deletion in adult mice was not lethal to hematopoiesis; rather, we observed a marked expansion of the hematopoietic stem and progenitor cell (HSPC) compartment, with increased self-renewal and impaired differentiation capacity in these cells. TAF1-null HSPCs failed to produce mature blood cells in chimeric mice; these cells also failed to up-regulate key differentiation genes when induced to differentiate in vitro. TAF1 loss not only disrupted TFIID assembly and chromatin recruitment, but also reduced RNAPII promoter-proximal pausing. Thus, HSPCs utilize distinct transcriptional regulatory mechanisms to undergo differentiation versus maintaining self-renewal.
2025-07-09 | GSE248656 | GEO
Project description:While many sequence-specific transcription factors (TFs) have been identified as key regulators of hematopoietic stem cell (HSC) lineage determination, the function of general TFs in HSC behavior is poorly understood. To evaluate the function of the TFIID subunit TAF1 in normal hematopoiesis, we generated Taf1 conditional knockout mice and identified an essential role of TAF1 in fetal erythropoiesis. Surprisingly, TAF1 deletion in adult mice was not lethal to hematopoiesis; rather, we observed a marked expansion of the hematopoietic stem and progenitor cell (HSPC) compartment, with increased self-renewal and impaired differentiation capacity in these cells. TAF1-null HSPCs failed to produce mature blood cells in chimeric mice; these cells also failed to up-regulate key differentiation genes when induced to differentiate in vitro. TAF1 loss not only disrupted TFIID assembly and chromatin recruitment, but also reduced RNAPII promoter-proximal pausing. Thus, HSPCs utilize distinct transcriptional regulatory mechanisms to undergo differentiation versus maintaining self-renewal.
2025-07-09 | GSE248655 | GEO
Project description:While many sequence-specific transcription factors (TFs) have been identified as key regulators of hematopoietic stem cell (HSC) lineage determination, the function of general TFs in HSC behavior is poorly understood. To evaluate the function of the TFIID subunit TAF1 in normal hematopoiesis, we generated Taf1 conditional knockout mice and identified an essential role of TAF1 in fetal erythropoiesis. Surprisingly, TAF1 deletion in adult mice was not lethal to hematopoiesis; rather, we observed a marked expansion of the hematopoietic stem and progenitor cell (HSPC) compartment, with increased self-renewal and impaired differentiation capacity in these cells. TAF1-null HSPCs failed to produce mature blood cells in chimeric mice; these cells also failed to up-regulate key differentiation genes when induced to differentiate in vitro. TAF1 loss not only disrupted TFIID assembly and chromatin recruitment, but also reduced RNAPII promoter-proximal pausing. Thus, HSPCs utilize distinct transcriptional regulatory mechanisms to undergo differentiation versus maintaining self-renewal.
2025-07-09 | GSE248654 | GEO
Project description:TAF1, the largest subunit of TFIID, is dispensable for adult hematopoiesis [ATAC-Seq]
| PRJNA1045513 | ENA
Project description:TAF1, the largest subunit of TFIID, is dispensable for adult hematopoiesis [RNA-Seq]
| PRJNA1045523 | ENA
Project description:TAF1, the largest subunit of TFIID, is dispensable for adult hematopoiesis [ChIP-Seq]
| PRJNA1045516 | ENA
Project description:TAF1, the largest subunit of TFIID, is dispensable for adult hematopoiesis [scRNA-Seq]
| PRJNA1045526 | ENA
Project description:Large heteromeric multiprotein complexes play pivotal roles at every step of gene expression in eukaryotic cells. Among them, the 20-subunits basal transcription factor TFIID nucleates RNA polymerase II preinitiation complex at gene promoters. Here, by combining systematic RNA-immunoprecipitation experiments, single-molecule imaging, proteomics and structure-function analyses, we show that TFIID is built using co-translational assembly. We discovered that all early steps of TFIID assembly, involving protein heterodimerization, happen during protein synthesis. Strikingly, we identify TAF1 – the largest protein in the complex – as a flexible scaffold subunit that co-translationally recruits preassembled TFIID submodules found populating the cytoplasm of cells. Consequently, TAF1 depletion leads to a cytoplasmic accumulation of TFIID building blocks. Altogether, our data suggest a multistep hierarchical model for TFIID biogenesis that culminates with the co-translational assembly on nascent TAF1 polypeptide, that works as a ‘driver’ subunit. We envision that this assembly strategy could be shared with other large heteromeric protein complexes.
2023-07-04 | PXD036358 | Pride