Article: Antagonistic Interactions between Ikaros and the Chromatin Remodeler Mi-2 beta Determine Silencer Activity and Cd4 Gene Expression

• Published in: Immunity (Cambridge, Mass.) Mass.), 2007-11, Vol.27 (5), p.723-734
• Main Authors: Naito, Taku, Arco, Pablo Gomez-del, Williams, Christine J, Georgopoulos, Katia
• Format: Article
• Language: English
• ISSN: 1074-7613
• DOI: 10.1016/j.immuni.2007.09.008

Lineage commitment is induced by changes in gene expression dictated by the intimate interaction between transcription factors and chromatin regulators. Here, we revealed the antagonistic interplay between Ikaros and its associate the chromatin remodeler Mi-2 beta during T cell development, as exemplified by the regulation of Cd4 expression. Loss of Ikaros or Mi-2 beta led to activation or repression, respectively, of the Cd4 locus at inappropriate stages of development. Their combined mutation reverted to normal CD4 expression. In double-negative thymocytes, Ikaros binding to the Cd4 silencer contributed to its repressive activity. In double-positive thymocytes, concomitant binding of Mi-2 beta with Ikaros to the Cd4 silencer caused silencer inactivation, thereby allowing for CD4 expression. Mi-2 beta facilitated recruitment of histone acetyl transferases to the silencer. This recruitment possibly antagonized Ikaros and associated repressive activities. Thus, concomitant interactions between functionally opposing chromatin-regulating machineries are an important mode of gene regulation during lineage determination.