A homeotic mutation in the trithorax SET domain impedes histone binding

Trithorax (TRX) is a Drosophila SET domain protein that is required for the correct expression of homeotic genes. Here, we show that the TRX SET domai n efficiently binds to core histones. and nucleosomes. The primary target f or the SET domain is histone H3 and binding requires the N-terminal histone tails. The previously described trx(Z11) mutation changes a strictly conse rved glycine in the SET domain to serine and causes homeotic transformation s in the fly. We found that this mutation selectively interferes with histo ne binding, suggesting that histones represent a critical target during dev elopmental gene regulation by TRX.