The General Transcription Factor TAF7 is Essential for Embryonic Development but Not Essential for the Survival or Differentiation of Mature T Cells
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE34796 | GEO | 2012/04/01
SECONDARY ACCESSION(S): PRJNA151041
REPOSITORIES: GEO
Similar Datasets
Project description:TAF7, a component of the TFIID complex that nucleates the assembly of transcription preinitiation complexes, also independently interacts with and regulates the enzymatic activities of other transcription factors, including P-TEFb, TFIIH, and CIITA, ensuring an orderly progression in transcription initiation. Since not all TAFs are required in terminally differentiated cells, we examined the essentiality of TAF7 in cells at different developmental stages in vivo. Germ line disruption of the TAF7 gene is embryonic lethal between 3.5 and 5.5 days postcoitus. Mouse embryonic fibroblasts with TAF7 deleted cease transcription globally and stop proliferating. In contrast, whereas TAF7 is essential for the differentiation and proliferation of immature thymocytes, it is not required for subsequent, proliferation-independent differentiation of lineage committed thymocytes or for their egress into the periphery. TAF7 deletion in peripheral CD4 T cells affects only a small number of transcripts. However, T cells with TAF7 deleted are not able to undergo activation and expansion in response to antigenic stimuli. These findings suggest that TAF7 is essential for proliferation but not for proliferation-independent differentiation.
| S-EPMC3347399 | biostudies-literature
Project description:This SuperSeries is composed of the following subset Series: GSE34793: The General Transcription Factor TAF7 is Essential for Embryonic Development but Not Essential for the Survival or Differentiation of Mature T Cells (MEF data) GSE34795: The General Transcription Factor TAF7 is Essential for Embryonic Development but Not Essential for the Survival or Differentiation of Mature T Cells (T cell data) Refer to individual Series
2012-03-31 | E-GEOD-34796 | biostudies-arrayexpress
Project description:TAF7, a component of the TFIID complex that nucleates the assembly of transcription preinitiation complexes, also independently interacts with and regulates the enzymatic activities of other transcription factors, including P-TEFb, TFIIH and CIITA, ensuring an orderly progression in transcription initiation. Since not all TAFs are required in terminally differentiated cells, we examined the essentiality of TAF7 in cells at different developmental stages in vivo. Germ-line disruption of the TAF7 gene is embryonic lethal between 3.5 and 5.5 days post coitus. TAF7-deleted mouse embryonic fibroblasts (MEFs) globally cease transcription and stop proliferating. In contrast, whereas TAF7 is essential for the differentiation and proliferation of immature thymocytes, it is not required for subsequent, proliferation-independent differentiation of lineage committed thymocytes or their egress into the periphery. TAF7 deletion in peripheral CD4+ T cells affects only a small number of transcripts. However, TAF7-deleted T cells are not able to undergo activation and expansion in response to antigenic stimuli. These findings suggest that TAF7 is essential for proliferation but not for proliferation-independent differentiation.
2012-04-01 | GSE34793 | GEO
Project description:TAF7, a component of the TFIID complex that nucleates the assembly of transcription preinitiation complexes, also independently interacts with and regulates the enzymatic activities of other transcription factors, including P-TEFb, TFIIH and CIITA, ensuring an orderly progression in transcription initiation. Since not all TAFs are required in terminally differentiated cells, we examined the essentiality of TAF7 in cells at different developmental stages in vivo. Germ-line disruption of the TAF7 gene is embryonic lethal between 3.5 and 5.5 days post coitus. TAF7-deleted mouse embryonic fibroblasts (MEFs) globally cease transcription and stop proliferating. In contrast, whereas TAF7 is essential for the differentiation and proliferation of immature thymocytes, it is not required for subsequent, proliferation-independent differentiation of lineage committed thymocytes or their egress into the periphery. TAF7 deletion in peripheral CD4+ T cells affects only a small number of transcripts. However, TAF7-deleted T cells are not able to undergo activation and expansion in response to antigenic stimuli. These findings suggest that TAF7 is essential for proliferation but not for proliferation-independent differentiation.
2012-04-01 | GSE34795 | GEO
Project description:TAF7, a component of the TFIID complex that nucleates the assembly of transcription preinitiation complexes, also independently interacts with and regulates the enzymatic activities of other transcription factors, including P-TEFb, TFIIH and CIITA, ensuring an orderly progression in transcription initiation. Since not all TAFs are required in terminally differentiated cells, we examined the essentiality of TAF7 in cells at different developmental stages in vivo. Germ-line disruption of the TAF7 gene is embryonic lethal between 3.5 and 5.5 days post coitus. TAF7-deleted mouse embryonic fibroblasts (MEFs) globally cease transcription and stop proliferating. In contrast, whereas TAF7 is essential for the differentiation and proliferation of immature thymocytes, it is not required for subsequent, proliferation-independent differentiation of lineage committed thymocytes or their egress into the periphery. TAF7 deletion in peripheral CD4+ T cells affects only a small number of transcripts. However, TAF7-deleted T cells are not able to undergo activation and expansion in response to antigenic stimuli. These findings suggest that TAF7 is essential for proliferation but not for proliferation-independent differentiation. We previously provided evidence that TAF7 is a regulator of the early steps of transcription initiation, that it affects the expression of about 65% of transcripts in 293 kidney cells, and of those, some are TAF1-dependent while others are TAF1-independent. Therefore, we next asked whether TAF7 is dispensable for a subset of embryonic fibroblast genes or whether it is required globally. Both TAF7f/f and TAF7+/+ MEF lines were infected by MSCV Cre-GFP retroviruses, and the infected cells (GFP+) were isolated by FACS at 24, 48 and 72 hours post infection. Uninfected cells from each line were harvested at the same time, collected by FACS and processed simultaneously to be used as controls. The experiments were performed in triplicate. All RNAs were extracted using shredders and the Qiagen RNeasy mini kit and their quality assayed before using for hybridization. Total RNA from each of the triplicates was hybridized on the Affymetrix exon array. All exon array data were analyzed with Affymetrix Expression Console SoftwareTM (version 1.1). The Robust Multi-array Analysis (RMA) algorithm was used for gene intensity analysis. Only genes in the M-bM-^@M-^\coreM-bM-^@M-^] set, which represents RefSeq and full-length GenBank mRNAs, were included in the analysis.
2012-03-31 | E-GEOD-34793 | biostudies-arrayexpress
Project description:TAF7, a component of the TFIID complex that nucleates the assembly of transcription preinitiation complexes, also independently interacts with and regulates the enzymatic activities of other transcription factors, including P-TEFb, TFIIH and CIITA, ensuring an orderly progression in transcription initiation. Since not all TAFs are required in terminally differentiated cells, we examined the essentiality of TAF7 in cells at different developmental stages in vivo. Germ-line disruption of the TAF7 gene is embryonic lethal between 3.5 and 5.5 days post coitus. TAF7-deleted mouse embryonic fibroblasts (MEFs) globally cease transcription and stop proliferating. In contrast, whereas TAF7 is essential for the differentiation and proliferation of immature thymocytes, it is not required for subsequent, proliferation-independent differentiation of lineage committed thymocytes or their egress into the periphery. TAF7 deletion in peripheral CD4+ T cells affects only a small number of transcripts. However, TAF7-deleted T cells are not able to undergo activation and expansion in response to antigenic stimuli. These findings suggest that TAF7 is essential for proliferation but not for proliferation-independent differentiation. The T cells are purified spleen CD4+ T cells coming either from TAF7f/- 8EIII-cre+ (TAF7 -/-) or TAF7 f/- 8EIII-cre - (TAF7+/-). The cells were purified by FACS based on cell surface marker expression: high TCRbeta and CD4 expression. The cells are enriched in naive CD4 T cells based on their low level of CD44 surface expression. All RNAs were extracted using shredders and the Qiagen RNeasy mini kit and their quality assayed before using for hybridization. Total RNA was hybridized on the Affymetrix exon array. All exon array data were analyzed with Affymetrix Expression Console SoftwareTM (version 1.1). The Robust Multi-array Analysis (RMA) algorithm was used for gene intensity analysis. Only genes in the "core" set, which represents RefSeq and full-length GenBank mRNAs, were included in the analysis.
2012-03-31 | E-GEOD-34795 | biostudies-arrayexpress
Project description:TEAD1 (TEA domain transcription factor 1), a transcription factor known for the functional output of Hippo signaling, is important for tumorigenesis. However, the role of TEAD1 in the development of vascular smooth muscle cell (VSMC) is unknown. To investigate cell-specific role of Tead1, we generated cardiomyocyte (CMC) and VSMC-specific Tead1 knockout mice. We found CMC/VSMC-specific deletion of Tead1 led to embryonic lethality by E14.5 in mice due to hypoplastic cardiac and vascular walls, as a result of impaired CMC and VSMC proliferation. Whole transcriptome analysis revealed that deletion of Tead1 in CMCs/VSMCs downregulated expression of muscle contractile genes and key transcription factors including Pitx2c and myocardin. In vitro studies demonstrated that PITX2c and myocardin rescued TEAD1-dependent defects in VSMC differentiation. We further identified Pitx2c as a novel transcriptional target of TEAD1, and PITX2c exhibited functional synergy with myocardin by directly interacting with myocardin, leading to augment the differentiation of VSMC. In summary, our study reveals a critical role of Tead1 in cardiovascular development in mice, but also identifies a novel regulatory mechanism, whereby Tead1 functions upstream of the genetic regulatory hierarchy for establishing smooth muscle contractile phenotype.
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Project description:Heat shock factor binding protein 1 (HSBP1) is a 76 amino acid polypeptide that contains two arrays of hydrophobic heptad repeats and was originally identified through its interaction with the oligomerization domain of heat shock factor 1 (Hsf1), suppressing Hsf1's transcriptional activity following stress. To examine the function of HSBP1 in vivo, we generated mice with targeted disruption of the hsbp1 gene and examined zebrafish embryos treated with HSBP1-specific morpholino oligonucleotides. Our results show that hsbp1 is critical for preimplantation embryonic development. Embryonic stem (ES) cells deficient in hsbp1 survive and proliferate normally into the neural lineage in vitro; however, lack of hsbp1 in embryoid bodies (EBs) leads to disorganization of the germ layers and a reduction in the endoderm-specific markers (such as α-fetoprotein). We further show that hsbp1-deficient mouse EBs and knockdown of HSBP1 in zebrafish leads to an increase in the expression of the neural crest inducers Snail2, Tfap2α and Foxd3, suggesting a potential role for HSBP1 in the Wnt pathway. The hsbp1-deficient ES cells, EBs and zebrafish embryos with reduced HSBP1 levels exhibit elevated levels of Hsf1 activity and expression of heat shock proteins (Hsps). We conclude that HSBP1 plays an essential role during early mouse and zebrafish embryonic development.
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Project description:[Figure: see text].
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Project description:Nonsense-mediated mRNA decay (NMD) is a highly conserved post-transcriptional gene expression regulatory mechanism in eukaryotic cells. NMD eliminates aberrant mRNAs with premature termination codons to surveil transcriptome integrity. Furthermore, NMD fine-tunes gene expression by destabilizing RNAs with specific NMD features. Thus, by controlling the quality and quantity of the transcriptome, NMD plays a vital role in mammalian development, stress response, and tumorigenesis. Deficiencies of NMD factors result in early embryonic lethality, while the underlying mechanisms are poorly understood. SMG5 is a key NMD factor. In this study, we generated an Smg5 conditional knockout mouse model and found that Smg5-null results in early embryonic lethality before E13.5. Furthermore, we produced multiple lines of Smg5 knockout mouse embryonic stem cells (mESCs) and found that the deletion of Smg5 in mESCs does not compromise cell viability. Smg5-null delays differentiation of mESCs. Mechanistically, our study reveals that the c-MYC protein, but not c-Myc mRNA, is upregulated in SMG5-deficient mESCs. The overproduction of c-MYC protein could be caused by enhanced protein synthesis upon SMG5 loss. Furthermore, SMG5-null results in dysregulation of alternative splicing on multiple stem cell differentiation regulators. Overall, our findings underscore the importance of SMG5-NMD in regulating mESC cell-state transition.
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