Ikaros DNA-binding proteins direct formation of chromatin remodeling complexes in lymphocytes.
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.
Kim
J
J
Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown 02129, USA.
Sif
S
S
Jones
B
B
Jackson
A
A
Koipally
J
J
Heller
E
E
Winandy
S
S
Viel
A
A
Sawyer
A
A
Ikeda
T
T
Kingston
R
R
Georgopoulos
K
K
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D001324:Autoantigens / Q000502:physiology; D002352:Carrier Proteins / Q000502:physiology; D002458:Cell Fractionation; D002843:Chromatin / Q000378:metabolism*; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000502:physiology*; D029721:Drosophila Proteins; D016193:G1 Phase / Q000276:immunology; D006655:Histone Deacetylases / Q000378:metabolism; D051740:Ikaros Transcription Factor; D046911:Macromolecular Substances; D051379:Mice; D008817:Mice, Mutant Strains; D009687:Nuclear Proteins / Q000378:metabolism; D009707:Nucleosomes / Q000378:metabolism; D016196:S Phase / Q000276:immunology; D013154:Spleen; D013601:T-Lymphocytes / Q000378:metabolism*; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D016335:Zinc Fingers / Q000502:physiology
D001324:Autoantigens; D002352:Carrier Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C491396:Ikzf3 protein, mouse; D046911:Macromolecular Substances; C116095:Mi-2 protein, Drosophila; D009687:Nuclear Proteins; D009707:Nucleosomes; D015534:Trans-Activators; D014157:Transcription Factors; C497238:Zfpn1a1 protein, mouse; D051740:Ikaros Transcription Factor; D006655:Histone Deacetylases; D000251:Adenosine Triphosphatases; C513194:Smarca4 protein, mouse; D004265:DNA Helicases