Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The transcription factor Zfp281 serves redundantly with Zfp148 to support CD4+ T cell development and functions [Papain multiome]

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE227330 | GEO | 2023/11/13

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

The transcription factor Zfp281 serves redundantly with Zfp148 to support CD4+ T cell development and functions [Th2 ChIP]

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

The transcription factor Zfp281 serves redundantly with Zfp148 to support CD4+ T cell development and functions [scRNA-seq]

2023-11-13 | GSE206521 | GEO

The transcription factor Zfp281 serves redundantly with Zfp148 to support CD4+ T cell development and functions [Thymus Visium]

2023-11-13 | GSE227332 | GEO

The transcription factor Zfp281 serves redundantly with Zfp148 to support CD4+ T cell development and functions [Population RNA-seq]

2023-11-13 | GSE206542 | GEO

Zfp281 and Zfp148 control CD4+ T cell thymic development and Th2 functions. (ChIP-seq)

Project description:How CD4+-lineage gene expression is initiated in differentiating thymocytes remains poorly understood. Here, we show that the paralog transcription factors Zfp281 and Zfp148 control both this process and cytokine expression by Th2 effector cells. Genetic, single-cell, and spatial transcriptomic analyses show that these factors promote the intrathymic CD4+ T cell differentiation of MHC II-restricted thymocytes, including expression of the CD4+ lineage-committing factor Thpok. In peripheral T cells, Zfp281 and Zfp148 promote chromatin opening at and expression of Th2 cytokine genes, but not of the Th2 lineage determining transcription factor Gata3. Zfp281 interacts with Gata3, and binds Gata3 genomic binding sites at loci encoding Thpok and Th2 cytokines. Thus, Zfp148 and Zfp281 collaborate with Gata3 to promote CD4+ T cell development and Th2 cell responses.

2023-11-13 | GSE207469 | GEO

Zfp281 and Zfp148 control CD4+ T cell thymic development and Th2 functions

Project description:How CD4+ lineage gene expression is initiated in differentiating thymocytes remains poorly understood. Here, we show that the paralog transcription factors Zfp281 and Zfp148 control both this process and cytokine expression by T helper cell type 2 (TH2) effector cells. Genetic, single-cell, and spatial transcriptomic analyses showed that these factors promote the intrathymic CD4+ T cell differentiation of class II major histocompatibility complex (MHC II)–restricted thymocytes, including expression of the CD4+ lineage–committing factor Thpok. In peripheral T cells, Zfp281 and Zfp148 promoted chromatin opening at and expression of TH2 cytokine genes but not of the TH2 lineage–determining transcription factor Gata3. We found that Zfp281 interacts with Gata3 and is recruited to Gata3 genomic binding sites at loci encoding Thpok and TH2 cytokines. Thus, Zfp148 and Zfp281 collaborate with Gata3 to promote CD4+ T cell development and TH2 cell responses. This SuperSeries is composed of the SubSeries listed below.

2023-11-10 | GSE207572 | GEO

ChIP-seq data for zfp148 and zfp281 chromatin occupancy in hemin-induced human K562 cells

Project description:ChIP-seq was carried for zfp148 and zfp281 in human K562 cells to test the hypothesis that these two transcription factor family members play overlapping roles in erythropoiesis.

2019-09-03 | GSE121133 | GEO

Genome-wide gene expression profiling revealed a critical role for GATA3 in the maintenance of the Th2 cell identity

Project description:Functionally polarized CD4+ T helper (Th) cells such as Th1, Th2 and Th17 cells are central to the regulation of acquired immunity. However, the molecular mechanisms governing the maintenance of the polarized functions of Th cells remain unclear. GATA3, a master regulator of Th2 cell differentiation, initiates the expressions of Th2 cytokine genes and other Th2-specific genes. GATA3 also plays important roles in maintaining Th2 cell function and in continuous chromatin remodeling of Th2 cytokine gene loci. However, it is unclear whether continuous expression of GATA3 is required to maintain the expression of various other Th2-specific genes. In this report, genome-wide DNA gene expression profiling revealed that GATA3 expression is critical for the expression of a certain set of Th2-specific genes. We demonstrated that GATA3 dependency is reduced for some Th2-specific genes in fully developed Th2 cells compared to that observed in effector Th2 cells, whereas it is unchanged for other genes. Moreover, effects of a loss of GATA3 expression in Th2 cells on the expression of cytokine and cytokine receptor genes were examined in detail. A critical role of GATA3 in the regulation of Th2-specific gene expression is confirmed in in vivo generated antigen-specific memory Th2 cells. Therefore, GATA3 is required for the continuous expression of the majority of Th2-specific genes involved in maintaining the Th2 cell identity. Mock-transfected and GATA3 siRNA-transfected Th2 and Th2-4th cells are profiled for mRNA expression

2013-04-19 | E-GEOD-46185 | biostudies-arrayexpress

Transcription factor Zfp281 sustains CD4+ T lymphocyte activation by directly repressing Ctla-4 transcription

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

Genome-wide gene expression profiling revealed a critical role for GATA3 in the maintenance of the Th2 cell identity

2013-04-19 | GSE46185 | GEO