Histone modifications are required to gain access to DNA sequences within the tightly compacted genome and enable gene transcription. It has been proposed that acetylation of the amino-terminal tails of the core histones within the nucleosome particle is critical for activating transcription. In the December Genes and Development, Nowak and Corces suggest that histone phosphorylation may play a greater role than acetylation in gene induction (Genes Dev 2000, 14:3003-3013). They studied the heat shock response in Drosophila melanogaster and the role of histone modification using immunocytochemical analysis of polytene chromosomes. Heat shock causes a general repression of gene expression and a rapid induction of specific heat shock genes. Acetylation of core histones H3 and H4 did not change during the heat shock response. In contrast, antibodies recognizing phosphorylated histone H3 tails revealed dramatic changes in phosphorylation associated with the transcriptional response to heat shock.