title: Selective regulation of lymphopoiesis and leukemogenesis by individual zinc fingers of Ikaros.
abstract: C2H2 zinc fingers are found in several key transcriptional regulators in the immune system. However, these proteins usually contain more fingers than are needed for sequence-specific DNA binding, which suggests that different fingers regulate different genes and functions. Here we found that mice lacking finger 1 or finger 4 of Ikaros exhibited distinct subsets of the hematological defects of Ikaros-null mice. Most notably, the two fingers controlled different stages of lymphopoiesis, and finger 4 was selectively required for tumor suppression. The distinct defects support the hypothesis that only a small number of genes that are targets of Ikaros are critical for each of its biological functions. The subcategorization of functions and target genes by mutagenesis of individual zinc fingers will facilitate efforts to understand how zinc-finger transcription factors regulate development, immunity and disease.
authors.affiliation: 1] Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California, USA. [2] Molecular Biology Institute, University of California, Los Angeles, California, USA. [3].
authors.forename: Hilde
authors.identifier: 0000000192873375
authors.initials: H
authors.lastname: Schjerven
authors.forename: Jami
authors.initials: J
authors.lastname: McLaughlin
authors.forename: Teresita L
authors.initials: TL
authors.lastname: Arenzana
authors.forename: Seth
authors.initials: S
authors.lastname: Frietze
authors.forename: Donghui
authors.initials: D
authors.lastname: Cheng
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Wadsworth
authors.forename: Gregory W
authors.initials: GW
authors.lastname: Lawson
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Bensinger
authors.forename: Peggy J
authors.initials: PJ
authors.lastname: Farnham
authors.forename: Owen N
authors.initials: ON
authors.lastname: Witte
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Smale
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D047369:Chromatin Immunoprecipitation; D016000:Cluster Analysis; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D018095:Germ-Line Mutation; D059014:High-Throughput Nucleotide Sequencing; D051740:Ikaros Transcription Factor / Q000235:genetics* / Q000378:metabolism; D016130:Immunophenotyping; D007938:Leukemia / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D008223:Lymphoma / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D038041:Lymphopoiesis / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D059372:Nucleotide Motifs; D010641:Phenotype; D056510:Position-Specific Scoring Matrices; D011485:Protein Binding; D060168:Thymocytes / Q000378:metabolism
chemical_list: C497238:Zfpn1a1 protein, mouse; D051740:Ikaros Transcription Factor; D016044:Fusion Proteins, bcr-abl