Selective regulation of lymphopoiesis and leukemogenesis by individual zinc fingers of Ikaros

Hilde Schjerven, Jami Mclaughlin, Teresita L. Arenzana, Seth Frietze, Donghui Cheng, Sarah E. Wadsworth, Gregory W. Lawson, Steven J. Bensinger, Peggy J. Farnham, Owen N. Witte, Stephen T. Smale

Research output: Contribution to journalArticle

61 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1073-1083
Number of pages11
JournalNature Immunology
Volume14
Issue number10
DOIs
StatePublished - 2013
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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