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Gene expression profiling of mature CD4 SP thymocytes from a mouse strain with an ENU-induced mutation in Zfp335

ABSTRACT: The generation of naïve T lymphocytes is critical for immune function yet the mechanisms governing their maturation remain incompletely understood. We have identified a mouse mutant, bloto, that harbors a hypomorphic mutation in the zinc finger protein Zfp335. Mutant blt/blt mice exhibit a naïve T cell deficiency due to an intrinsic developmental defect that begins to manifest in the thymus and continues into the periphery, affecting T cells that have recently undergone thymic egress. Zfp335 binds to promoter regions via a consensus motif, and its target genes are enriched in categories related to protein metabolism, mitochondrial function and transcriptional regulation. Restoring the expression of one target, Ankle2, partially rescues T cell maturation. Our findings identify Zfp335 as a transcription factor and essential regulator of late-stage intrathymic and post-thymic T cell maturation.

ORGANISM(S): Mus musculus

PROVIDER: GSE58288 | GEO | 2014/10/17

SECONDARY ACCESSION(S): PRJNA251899

REPOSITORIES: GEO

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Gene expression profiling of recent thymic emigrants (RTEs) from a mouse strain with an ENU-induced mutation in Zfp335

Project description:The generation of naïve T lymphocytes is critical for immune function yet the mechanisms governing their maturation remain incompletely understood. We have identified a mouse mutant, bloto, that harbors a hypomorphic mutation in the zinc finger protein Zfp335. Mutant blt/blt mice exhibit a naïve T cell deficiency due to an intrinsic developmental defect that begins to manifest in the thymus and continues into the periphery, affecting T cells that have recently undergone thymic egress. Zfp335 binds to promoter regions via a consensus motif, and its target genes are enriched in categories related to protein metabolism, mitochondrial function and transcriptional regulation. Restoring the expression of one target, Ankle2, partially rescues T cell maturation. Our findings identify Zfp335 as a transcription factor and essential regulator of late-stage intrathymic and post-thymic T cell maturation.

2014-10-17 | GSE58289 | GEO

Gene expression profiling of mature CD4 SP thymocytes from a mouse strain with an ENU-induced mutation in Zfp335

Project description:The generation of naM-CM-/ve T lymphocytes is critical for immune function yet the mechanisms governing their maturation remain incompletely understood. We have identified a mouse mutant, bloto, that harbors a hypomorphic mutation in the zinc finger protein Zfp335. Mutant blt/blt mice exhibit a naM-CM-/ve T cell deficiency due to an intrinsic developmental defect that begins to manifest in the thymus and continues into the periphery, affecting T cells that have recently undergone thymic egress. Zfp335 binds to promoter regions via a consensus motif, and its target genes are enriched in categories related to protein metabolism, mitochondrial function and transcriptional regulation. Restoring the expression of one target, Ankle2, partially rescues T cell maturation. Our findings identify Zfp335 as a transcription factor and essential regulator of late-stage intrathymic and post-thymic T cell maturation. WT and blt/blt mature CD4SP thymocytes were sorted from mixed hematopoietic chimeras for RNA extraction and gene expression analysis on Affymetrix arrays. 6 samples were analyzed in total, with 3 biological replicates per genotype.

2014-10-17 | E-GEOD-58288 | biostudies-arrayexpress

Gene expression profiling of recent thymic emigrants (RTEs) from a mouse strain with an ENU-induced mutation in Zfp335

Project description:The generation of naM-CM-/ve T lymphocytes is critical for immune function yet the mechanisms governing their maturation remain incompletely understood. We have identified a mouse mutant, bloto, that harbors a hypomorphic mutation in the zinc finger protein Zfp335. Mutant blt/blt mice exhibit a naM-CM-/ve T cell deficiency due to an intrinsic developmental defect that begins to manifest in the thymus and continues into the periphery, affecting T cells that have recently undergone thymic egress. Zfp335 binds to promoter regions via a consensus motif, and its target genes are enriched in categories related to protein metabolism, mitochondrial function and transcriptional regulation. Restoring the expression of one target, Ankle2, partially rescues T cell maturation. Our findings identify Zfp335 as a transcription factor and essential regulator of late-stage intrathymic and post-thymic T cell maturation. WT and blt/blt CD4+ RTEs were sorted from mixed hematopoietic chimeras for RNA extraction and gene expression analysis on Affymetrix arrays. 6 samples were analyzed in total, with 3 biological replicates per genotype.

2014-10-17 | E-GEOD-58289 | biostudies-arrayexpress

Genome-wide profiling of Zfp335 binding sites in thymocytes

Project description:The generation of naM-CM-/ve T lymphocytes is critical for immune function yet the mechanisms governing their maturation remain incompletely understood. We have identified a mouse mutant, bloto, that harbors a hypomorphic mutation in the zinc finger protein Zfp335. Mutant blt/blt mice exhibit a naM-CM-/ve T cell deficiency due to an intrinsic developmental defect that begins to manifest in the thymus and continues into the periphery, affecting T cells that have recently undergone thymic egress. Zfp335 binds to promoter regions via a consensus motif, and its target genes are enriched in categories related to protein metabolism, mitochondrial function and transcriptional regulation. Restoring the expression of one target, Ankle2, partially rescues T cell maturation. Our findings identify Zfp335 as a transcription factor and essential regulator of late-stage intrathymic and post-thymic T cell maturation. 4 Zfp335 ChIP-seq samples and 2 input samples with WT vs. blt/blt thymocytes.

2014-10-17 | E-GEOD-58333 | biostudies-arrayexpress

Genome-wide profiling of Zfp335 binding sites in thymocytes

2014-10-17 | GSE58333 | GEO

Zfp335 establishes neonatal immune tolerance through safeguarding effector Treg lineage commitment and maintenance [ChIP-seq]

Project description:Regulatory T (Treg) cells are crucial for maintaining peripheral immune tolerance and preventing destructive autoreactive responses, but how heterogeneous Treg populations establish tolerant status remains unclear. Here, we found that Zinc finger protein 335 (Zfp335) is indispensable for the differentiation and maintenance of effector Treg (eTreg) population and immunological self-tolerance in neonates. Mice with Zfp335 deletion in Treg cells exhibit early-onset autoimmune disease with severe inflammation in multiple organs and unrestricted activation and expansion of conventional T cells. Zfp335-deficient Treg cells display dysfunctional and pathogenic features together with multiple defects in proliferation, survival and suppressive function. Importantly, our single-cell RNA sequencing (scRNA-seq) analyses reveal distinct Treg populations and that Zfp335 deficiency causes an almost complete loss of eTreg population along with significant accumulation of dysfunctional Treg populations. Mechanistically, Zfp335 controls both fate decision and homeostasis of eTreg cells by directly targeting genes associated with homeostasis and oxidation-fueled oxidative phosphorylation (OXPHOS) and PI3K-Akt-mTOR metabolic pathways. Our data establish the concept that Zfp335 serves as a checkpoint and safeguard for eTreg lineage commitment and maintenance.

2022-02-28 | GSE189076 | GEO

Loss of Zfp335 triggers cGAS/STING-dependent apoptosis of post-B-selection pre-T cells [TCRa-seq]

Project description:The transcription factor Zfp335 is esstential for the survival of post-B-selection DN4 thymocytes. We utilized TCRa repertoire sequencing to assess alterations to survival duration for Zfp335-deficient DP thymocytes.

2022-09-13 | GSE205323 | GEO

Loss of Zfp335 triggers cGAS/STING-dependent apoptosis of post-B-selection pre-T cells [RNA-seq]

Project description:The transcription factor Zfp335 is esstential for the survival of post-B-selection DN4 thymocytes. We utilized RNA-seq to profile the alterations to the transcriptional profiles of Zfp335-deficient DP thymocytes

2022-09-13 | GSE189242 | GEO

Gene Expression Profile during human CD4+ T cell differentiation

Project description:Subpopulations of human fetal thymocyte and circulating naïve T cells were obtained through FACS sorting, including CD3-CD4+CD8- intrathymic T progenitor cells (ITTP), CD3intCD4+CD8+ "double positive" thymocytes (DP), CD3highCD4+CD8- "single positive" thymocytes (SP4), CD3+CD4+CD8-CD45RA+CD62L+ naïve T cells from cord blood (CB4+), and CD3+CD4+CD8-CD45RA+CD62L+ naïve T cells from adult blood (AB4+). Keywords = Microarray Keywords = gene expression Keywords = thymocytes Keywords = naïve CD4+ T cell Keywords = recent thymic emigrants Keywords: other

2004-07-01 | GSE1460 | GEO

The C2H2-ZF transcription factor Zfp335 recognizes two consensus motifs using separate zinc finger arrays

Project description:The complexities of DNA recognition by transcription factors with multiple Cys2-His2 zinc fingers (C2H2-ZFs) remain poorly studied. We previously reported a mutation (R1092W) in the C2H2-ZF transcription factor Zfp335 which led to selective loss of binding at a subset of targets, although the basis for this was unclear. We show that Zfp335 binds DNA and drives transcription via recognition of two distinct consensus motifs by separate ZF clusters, and identify the specific motif interaction disrupted by R1092W. Our work presents Zfp335 as a model for understanding how C2H2-ZF TFs may utilize multiple recognition motifs to control gene expression.

2016-07-11 | GSE83116 | GEO

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