Ikaros DNA-binding Proteins Direct Formation of Chromatin Remodeling Complexes in Lymphocytes

Immunity. 1999 Mar;10(3):345-55. doi: 10.1016/s1074-7613(00)80034-5.

Abstract

The Ikaros gene family encodes zinc finger DNA-binding proteins essential for lineage determination and control of proliferation in the lymphoid system. Here, we report that, in the nucleus of a T cell, a major fraction of Ikaros and Aiolos proteins associate with the DNA-dependent ATPase Mi-2 and histone deacetylases, in a 2 MD complex. This Ikaros-NURD complex is active in chromatin remodeling and histone deacetylation. Upon T cell activation, Ikaros recruits Mi-2/HDAC to regions of heterochromatin. These studies reveal that Ikaros proteins are capable of targeting chromatin remodeling and deacetylation complexes in vivo. We propose that the restructuring of chromatin is a key aspect of Ikaros function in lymphocyte differentiation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphatases / metabolism
  • Animals
  • Autoantigens / physiology
  • Carrier Proteins / physiology
  • Cell Fractionation
  • Chromatin / metabolism*
  • DNA Helicases
  • DNA-Binding Proteins / physiology*
  • Drosophila Proteins*
  • G1 Phase / immunology
  • Histone Deacetylases / metabolism
  • Ikaros Transcription Factor
  • Macromolecular Substances
  • Mice
  • Mice, Mutant Strains
  • Nuclear Proteins / metabolism
  • Nucleosomes / metabolism
  • S Phase / immunology
  • Spleen
  • T-Lymphocytes / metabolism*
  • Trans-Activators / physiology
  • Transcription Factors / metabolism
  • Transcription Factors / physiology*
  • Zinc Fingers / physiology

Substances

  • Autoantigens
  • Carrier Proteins
  • Chromatin
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Ikzf3 protein, mouse
  • Macromolecular Substances
  • Mi-2 protein, Drosophila
  • Nuclear Proteins
  • Nucleosomes
  • Trans-Activators
  • Transcription Factors
  • Zfpn1a1 protein, mouse
  • Ikaros Transcription Factor
  • Histone Deacetylases
  • Adenosine Triphosphatases
  • Smarca4 protein, mouse
  • DNA Helicases