Transcription factor Zfp281 sustains CD4+ T lymphocyte activation by directly repressing Ctla-4 transcription
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ABSTRACT:
PROVIDER: PRJNA560862 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9995525.fastq.gz | Fastqsanger.gz | |||
| SRR9995526.fastq.gz | Fastqsanger.gz | |||
| SRR9995527.fastq.gz | Fastqsanger.gz | |||
| SRR9995528.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Expression of co-inhibitory receptors, such as CTLA-4, on effector T cells is a key mechanism for the negative regulation of T cell activation. However, how CTLA-4 is transcriptionally regulated is not well understood. Zfp281, a C2H2 zinc finger protein, is a negative regulator of maintaining pluripotency for embryonic stem cells. Nevertheless, its function in differentiated cells has not been studied. We generated Zfp281 conditional knockout mice in which the function of Zfp281 gene was conditionally disrupted by Cd4Cre transgene to study its impact on T cell function. Zfp281 was dispensable for T cell development, but CD4+ T cell activation and cytokine production were impaired due to diminished T cell receptor signaling. Furthermore, Zfp281 deficiency inhibited in vivo T cell responses to Listeria monocytogenes infection. Using genome-wide expression profiling assays, we determined that Zfp281 repressed Ctla-4 expression by directly binding GC-rich sites of its promoter, which inhibited the negative feedback of T cell activation. In line with this, CTLA-4 blockade and shRNA knock down can partly rescue the reduced cytokine production caused by Zfp281 deficiency. These findings identify that Zfp281 sustains CD4+ T lymphocyte activation by directly repressing Ctla-4 transcription.
2021-01-19 | GSE135968 | GEO
Project description:The expression of coinhibitory receptors, such as CTLA-4, on effector T cells is a key mechanism for the negative regulation of T-cell activation. However, the transcriptional regulation of CTLA-4 is not well understood. Zfp281, a C2H2 zinc finger protein, is a negative regulator of pluripotency maintenance of embryonic stem cells. Nevertheless, the function of Zfp281 in differentiated cells has not been studied. We generated Zfp281 conditional knockout mice in which the function of the Zfp281 gene was conditionally disrupted by the Cd4Cre transgene to study its impact on T cell function. Zfp281 had no effect on T-cell development, but CD4+ T cell activation and cytokine production were impaired due to diminished T-cell receptor signaling. Furthermore, Zfp281 deficiency inhibited in vivo T cell responses to Listeria monocytogenes infection. Using genome-wide expression profiling assays, we determined that Zfp281 repressed Ctla-4 expression by directly binding to GC-rich sites in its promoter, which inhibited the negative feedback of T cell activation. In line with this result, CTLA-4 blockade and shRNA knockdown partly rescued the reduced cytokine production caused by Zfp281 deficiency. These findings indicate that Zfp281 sustains CD4+ T lymphocyte activation by directly repressing Ctla-4 transcription.
| S-EPMC7784856 | biostudies-literature
Project description:The transcription factor Gata3 is essential both for CD4+ T cell development in the thymus and for the differentiation of Th2 cells, which mediate responses against extracellular parasites and contribute to asthma and allergies. Here we report that the transcription factor Zfp281, in part redundantly with its paralog Zfp148, cooperates with Gata3 to promote CD4+ T cell development and Th2 cell differentiation. Disruption of both factors in T cells resulted in reduced numbers of spleen CD4+ T cells. Additionally, we show that Zfp281 interacts with Gata3, and that Zfp281 binds to Th2 cytokine loci in Th2 cells. Finally, we found that Zfp148 and Zfp281 promote Th2 cytokine expression. During airway inflammation, Zfp148/281-deficient CD4+ T cells failed to express Th2 cytokines, despite normal expression of Gata3. Altogether our data identify Zfp148 and Zfp281 as essential for enabling Gata3 functions in both CD4+ T cell development and Th2 function.
2023-11-13 | GSE237865 | GEO
Project description:The transcription factor Gata3 is essential both for CD4+ T cell development in the thymus and for the differentiation of Th2 cells, which mediate responses against extracellular parasites and contribute to asthma and allergies. Here we report that the transcription factor Zfp281, in part redundantly with its paralog Zfp148, cooperates with Gata3 to promote CD4+ T cell development and Th2 cell differentiation. Disruption of both factors in T cells resulted in reduced numbers of spleen CD4+ T cells. Additionally, we show that Zfp281 interacts with Gata3, and that Zfp281 binds to Th2 cytokine loci in Th2 cells. Finally, we found that Zfp148 and Zfp281 promote Th2 cytokine expression. During airway inflammation, Zfp148/281-deficient CD4+ T cells failed to express Th2 cytokines, despite normal expression of Gata3. Altogether our data identify Zfp148 and Zfp281 as essential for enabling Gata3 functions in both CD4+ T cell development and Th2 function.
2023-11-13 | GSE227332 | GEO
Project description:The transcription factor Gata3 is essential both for CD4+ T cell development in the thymus and for the differentiation of Th2 cells, which mediate responses against extracellular parasites and contribute to asthma and allergies. Here we report that the transcription factor Zfp281, in part redundantly with its paralog Zfp148, cooperates with Gata3 to promote CD4+ T cell development and Th2 cell differentiation. Disruption of both factors in T cells resulted in reduced numbers of spleen CD4+ T cells. Additionally, we show that Zfp281 interacts with Gata3, and that Zfp281 binds to Th2 cytokine loci in Th2 cells. Finally, we found that Zfp148 and Zfp281 promote Th2 cytokine expression. During airway inflammation, Zfp148/281-deficient CD4+ T cells failed to express Th2 cytokines, despite normal expression of Gata3. Altogether our data identify Zfp148 and Zfp281 as essential for enabling Gata3 functions in both CD4+ T cell development and Th2 function.
2023-11-13 | GSE227330 | GEO
Project description:The transcription factor Gata3 is essential both for CD4+ T cell development in the thymus and for the differentiation of Th2 cells, which mediate responses against extracellular parasites and contribute to asthma and allergies. Here we report that the transcription factor Zfp281, in part redundantly with its paralog Zfp148, cooperates with Gata3 to promote CD4+ T cell development and Th2 cell differentiation. Disruption of both factors in T cells resulted in reduced numbers of spleen CD4+ T cells. Additionally, we show that Zfp281 interacts with Gata3, and that Zfp281 binds to Th2 cytokine loci in Th2 cells. Finally, we found that Zfp148 and Zfp281 promote Th2 cytokine expression. During airway inflammation, Zfp148/281-deficient CD4+ T cells failed to express Th2 cytokines, despite normal expression of Gata3. Altogether our data identify Zfp148 and Zfp281 as essential for enabling Gata3 functions in both CD4+ T cell development and Th2 function.
2023-11-13 | GSE206521 | GEO
Project description:Zfp281 is a partner protein of Nanog. To identify potential target genes of Zfp281, we generated Zfp281 null ESCs using gene targeting, and compared transcriptomic changes between multiple lines of wildtype, heterozygous and null ESCs. Total 8 ESC lines: 3 wildtype lines, 2 heterozygous lines, and 3 null lines.
2011-12-01 | E-GEOD-30293 | biostudies-arrayexpress
Project description:The transcription factor Gata3 is essential both for CD4+ T cell development in the thymus and for the differentiation of Th2 cells, which mediate responses against extracellular parasites and contribute to asthma and allergies. Here we report that the transcription factor Zfp281, in part redundantly with its paralog Zfp148, cooperates with Gata3 to promote CD4+ T cell development and Th2 cell differentiation. Disruption of both factors in T cells resulted in reduced numbers of spleen CD4+ T cells. Additionally, we show that Zfp281 interacts with Gata3, and that Zfp281 binds to Th2 cytokine loci in Th2 cells. Finally, we found that Zfp148 and Zfp281 promote Th2 cytokine expression. During airway inflammation, Zfp148/281-deficient CD4+ T cells failed to express Th2 cytokines, despite normal expression of Gata3. Altogether our data identify Zfp148 and Zfp281 as essential for enabling Gata3 functions in both CD4+ T cell development and Th2 function.
2023-11-13 | GSE206542 | GEO
Project description:The progression and transition between the naïve, formative, and primed pluripotent states are accompanied by a sharp activation of the de novo DNA methyltransferases and the reorganization of transcriptional and epigenetic landscapes. Here we identified Zinc Finger Protein 281 (ZFP281) as an essential factor in the formative-to-primed pluripotent state transition. Using a knockout mouse model and a knockin degron cell system, we revealed that transcription of Dnmt3a/3b depends on the activity of ZFP281 in embryonic stem cells, epiblast-like cells, and epiblast stem cells. Mechanically, chromatin-bound ZFP281 and DNA hydroxylase TET1 are decreased in the formative state but recovered in the primed state to compete with DNMT3A/3B for establishing the DNA methylation and gene expression programs of primed pluripotency. In addition, chromatin occupancy of ZFP281 and TET1 depend on the R-loop structures formed at the ZFP281 target gene promoters devoid of DNA methylation. Our study demonstrates a comprehensive role of ZFP281 in modulating DNA methylation and demethylation for the establishment and maintenance of primed pluripotency.
2023-12-14 | GSE227093 | GEO
Project description:The progression and transition between the naïve, formative, and primed pluripotent states are accompanied by a sharp activation of the de novo DNA methyltransferases and the reorganization of transcriptional and epigenetic landscapes. Here we identified Zinc Finger Protein 281 (ZFP281) as an essential factor in the formative-to-primed pluripotent state transition. Using a knockout mouse model and a knockin degron cell system, we revealed that transcription of Dnmt3a/3b depends on the activity of ZFP281 in embryonic stem cells, epiblast-like cells, and epiblast stem cells. Mechanically, chromatin-bound ZFP281 and DNA hydroxylase TET1 are decreased in the formative state but recovered in the primed state to compete with DNMT3A/3B for establishing the DNA methylation and gene expression programs of primed pluripotency. In addition, chromatin occupancy of ZFP281 and TET1 depend on the R-loop structures formed at the ZFP281 target gene promoters devoid of DNA methylation. Our study demonstrates a comprehensive role of ZFP281 in modulating DNA methylation and demethylation for the establishment and maintenance of primed pluripotency.
2023-12-14 | GSE226041 | GEO