title: Zinc finger protein Zfp335 is required for the formation of the naïve T cell compartment.
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. Zfp335(bloto/bloto) 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. The effects of Zfp335(bloto) are multigenic and cannot be attributed to altered thymic selection, proliferation or Bcl2-dependent survival. 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. These findings identify Zfp335 as a transcription factor and essential regulator of late-stage intrathymic and post-thymic T cell maturation.
authors.affiliation: Department of Microbiology and Immunology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States.
authors.forename: Brenda Y
authors.initials: BY
authors.lastname: Han
authors.affiliation: Department of Microbiology and Immunology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States.
authors.forename: Shuang
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Computer Science, Stanford University, Stanford, United States.
authors.forename: Chuan-Sheng
authors.initials: CS
authors.lastname: Foo
authors.affiliation: Department of Microbiology and Immunology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Horton
authors.affiliation: Department of Microbiology and Immunology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States.
authors.forename: Craig N
authors.initials: CN
authors.lastname: Jenne
authors.affiliation: Department of Microbiology and Immunology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States.
authors.forename: Susan R
authors.initials: SR
authors.lastname: Watson
authors.affiliation: Australian Phenomics Facility, John Curtin School of Medical Research, Australian National University, Canberra, Australia.
authors.forename: Belinda
authors.initials: B
authors.lastname: Whittle
authors.affiliation: Department of Immunology, John Curtin School of Medical Research, Australian National University, Canberra, Australia.
authors.forename: Chris C
authors.initials: CC
authors.lastname: Goodnow
authors.affiliation: Department of Microbiology and Immunology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States.
authors.forename: Jason G
authors.initials: JG
authors.lastname: Cyster
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005816:Genetic Complementation Test; D007113:Immunity, Innate; D008565:Membrane Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D014158:Transcription, Genetic; D016335:Zinc Fingers / Q000235:genetics* / Q000276:immunology
chemical_list: C000598774:Ankle2 protein, mouse; D008565:Membrane Proteins; D009687:Nuclear Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014157:Transcription Factors; C000598773:zinc finger protein 335, mouse; C052617:Bcl2 protein, mouse
keywords: ENU mutagenesis; T cell development; chromosomes; genes; immunology; mouse; t cells; thymocytes; transcription factors