GATA3 abundance is a critical determinant of T cell receptor beta allelic exclusion [GATA3 overexpression]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE115743 | GEO | 2018/06/14
REPOSITORIES: GEO
Similar Datasets
Project description:RNA-seq in GFP-positive and GFP-negative DN4 stage thymocytes isolated from GATA3-GFP fusion protein knock-in mouse
2018-06-14 | GSE115740 | GEO
Project description:GATA3 abundance is a critical determinant of T cell receptor beta allelic exclusion [GATA3 overexpression]
| PRJNA475906 | ENA
Project description:Allelic exclusion describes the essential immunological process by which feedback repression of sequential DNA rearrangements ensures that only one autosome expresses a functional T or B cell receptor. In wild-type mammals, approximately 60% of cells have recombined the DNA of one T cell receptor β (TCRβ) V-to-DJ-joined allele in a functional configuration, while the second allele has recombined only the DJ sequences; the other 40% of cells have recombined the V to the DJ segments on both alleles, with only one of the two alleles predicting a functional TCRβ protein. Here we report that the transgenic overexpression of GATA3 leads predominantly to biallelic TCRβ gene (Tcrb) recombination. We also found that wild-type immature thymocytes can be separated into distinct populations based on intracellular GATA3 expression and that GATA3LO cells had almost exclusively recombined only one Tcrb locus (that predicted a functional receptor sequence), while GATA3HI cells had uniformly recombined both Tcrb alleles (one predicting a functional and the other predicting a nonfunctional rearrangement). These data show that GATA3 abundance regulates the recombination propensity at the Tcrb locus and provide new mechanistic insight into the historic immunological conundrum for how Tcrb allelic exclusion is mediated.
| S-EPMC5452726 | biostudies-literature
Project description:GATA3 abundance is a critical determinant of T cell receptor beta allelic exclusion [GATA3-GFP]
| PRJNA475908 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-06-14 | GSE115745 | GEO
Project description:GATA3 abundance is a critical determinant of T cell receptor beta allelic exclusion
| PRJNA475904 | ENA
Project description:The inner ear utilizes sensory hair cells as mechano-electric transducers for sensing sound and balance. In mammals, these hair cells lack the capacity for regeneration. Unlike mammals, hair cells from non-mammalian vertebrates, such as birds, can be regenerated throughout the life of the organism making them a useful model for studying inner ear genetics pathways. The zinc finger transcription factor GATA3 is required for inner ear development and mutations cause sensory neural deafness in humans. In the avian cochlea GATA3 is expressed throughout the sensory epithelia; however, expression is limited to the striola of the utricle. The striola corresponds to an abrupt change in morphologically distinct hair cell types and a 180° shift in hair cell orientation. We used 3 complimentary approaches to identify potential downstream targets of GATA3 in the avian utricle. Specifically we used microarray expression profiling of GATA3 knockdown by siRNA and GATA3 over-expression treatments as well as direct comparisons of GATA3 expressing cells from the striola and non GATA3 expressing cells from the extra-striola. Dissociated sensory epithelia were plated in 96 well cultures, 5 wells per sample. 4 days post plating, ~ 30% confluency, cells were transfected with a pMES vector containing an internal ribosome entry site regulating expression of GATA3 and eGFP under control of a chick beta-actin promoter. Controls were transfected with a vector containing EGFP only. There are 2 biological samples and experiments include technical replicates as well as dye-switches for a total of 8 microarrays.
2010-06-24 | E-GEOD-14784 | biostudies-arrayexpress
Project description:The inner ear utilizes sensory hair cells as mechano-electric transducers for sensing sound and balance. In mammals, these hair cells lack the capacity for regeneration. Unlike mammals, hair cells from non-mammalian vertebrates, such as birds, can be regenerated throughout the life of the organism making them a useful model for studying inner ear genetics pathways. The zinc finger transcription factor GATA3 is required for inner ear development and mutations cause sensory neural deafness in humans. In the avian cochlea GATA3 is expressed throughout the sensory epithelia; however, expression is limited to the striola of the utricle. The striola corresponds to an abrupt change in morphologically distinct hair cell types and a 180° shift in hair cell orientation. We used 3 complimentary approaches to identify potential downstream targets of GATA3 in the avian utricle. Specifically we used microarray expression profiling of GATA3 knockdown by siRNA and GATA3 over-expression treatments as well as direct comparisons of GATA3 expressing cells from the striola and non GATA3 expressing cells from the extra-striola.
2009-12-25 | GSE14784 | GEO
Project description:T cell factor 1 (Tcf1) is the first T cell‒specific protein induced in multipotent progenitors following Notch signaling in the thymus, leading to the activation of two major target genes, Gata3 and Bcl11b. Tcf1 deficiency results in partial arrests in T cell development high apoptosis, and increased development of B cells and myeloid cells. Phenotypically, fully T cell‒committed, Tcf1-deficient thymocytes have promiscuous gene expression, an altered epigenetic profile and can de-differentiate into more immature thymocytes and non-T cells. Expressing Bcl11b in Tcf1-deficient cells rescues T cell development, but does not strongly suppress the development of non-T cells; in contrast, expressing Gata3 suppresses the development of non-T cells, but does not rescue T cell development. Thus, T cell development is controlled by a minimal transcription factor network involving Notch signaling, Tcf1, and the subsequent division of labor between Bcl11b and Gata3, thereby ensuring a properly regulated T cell gene expression program
2019-08-28 | GSE119469 | GEO
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