To a first approximation, each Hox gene is normally expressed in those regions that develop abnormally when that gene is mutated or absent. How does each Hox protein give a segment its permanent identity? All the Hox proteins are similar in their DNA-binding regions, but they are very different in the regions that interact with the other proteins with which the Hox proteins form transcriptional regulatory complexes. The different protein partners act together with the Hox proteins to dictate which DNA binding sites will be recognized, as well as whether the effect on transcription at those sites will be activation or repression. Acting in this way, the Hox proteins modulate the actions of many other transcription regulators. Hundreds of genes are under this type of Hox-modulated control, including genes for cell–cell signaling, transcriptional regulation, cell polarity, cell adhesion, cytoskeletal function, cell growth, and cell death, all conspiring (in ways that are not yet understood) to give each segment its distinctive Hox-dependent character.
Hox Genes are expressed according to their Order in the  Hox complex
How, then, is the expression of the Hox genes themselves regulated? The coding sequences of the eight Hox genes in the Antennapedia and Bithorax complexes in Drosophila are interspersed amid a much larger quantity of regulatory DNA. This DNA includes binding sites for the products of the egg-polarity and segmentation genes, thereby serving as an interpreter of the multiple items of spatial information supplied to it by all these transcription regulators. The net result is that the particular set of Hox genes transcribed is appropriate for each location along the A-P body axis.
The pattern of Hox gene expression exhibits a remarkable regularity that suggests an additional form of control. The sequence in which the genes are ordered along the chromosome, in both the Antennapedia and the Bithorax complexes, corresponds almost exactly to the order in which they are expressed along the A-P axis of the body (Figure 21–24). This hints at some process of gene activation, perhaps dependent on chromatin structures that propagate along the Hox complexes, switching on one Hox gene after another according to their order along the chromosome. The most “posterior” of the Hox genes that are expressed in a cell generally dominates, driving down expression and activity of the “anterior” genes and dictating the character of the segment. The gene regulatory mechanisms underlying these phenomena are still not well understood, but their consequences are profound. We shall see that the serial organization of gene expression in the Hox complex is a fundamental feature that has been highly conserved in the course of animal evolution.
trithorax and polycomb Group proteins enable the Hox complexes to Maintain a permanent record of positional Information
The spatial pattern of expression of the genes in the Hox complex is set up by signals acting early in development, but the consequences are long lasting. Although the pattern of expression undergoes complex adjustments as development proceeds, the Hox complexes serve to stamp each cell and its progeny with a permanent record of the A-P position that the cell occupied in the early embryo. In this way, the cells of each segment are equipped with a long-term memory of their location along the A-P axis of the body. This memory trace is somehow imprinted on the Hox complexes, and it governs the segment-specific identity not only of the larval segments, but also of the structures of the adult fly.
The molecular mechanism of this memory of positional information relies on two types of regulation. One is from the Hox genes themselves: many of the Hox proteins autoactivate the transcription of their own genes, thereby helping to keep the genes on indefinitely. Another crucial input is from two large, complementary sets of proteins, called the Trithorax group and the Polycomb group, which stamp the chromatin of the Hox complex with a heritable record of its embryonic state of activation or repression. These are key general regulators of chromatin structure that can be shown to be critical for cell memory: if genes of the Trithorax or Polycomb group are defective, the pattern of expression of the Hox genes is set up correctly at first, but it is not correctly maintained as the embryo grows older.