We have seen in the preceding discussion how combinations of transcription factors that bind to specific DNA regulatory sequences control the transcription of eukaryotic genes. Whether or not a specific gene in a multicellular organism is expressed in a particular cell at a particular time is largely a consequence of the nuclear concentrations and activities of the transcription factors that interact with the transcription-control regions of that gene. (Exceptions are due to the “transcriptional memory” that results from the epigenetic mechanisms discussed in the next section.) Which transcription factors are expressed in a particular cell type, and the amounts produced, are determined by multiple regulatory interactions between transcription factors and control regions in genes encoding transcription factors that occur during the development and differentiation of that cell type. Recent advances in the analysis of transcription-factor-binding sites through identification of DNase I hypersensitive sites on a genomic scale have given us the first high-resolution view of how transcription-factor binding changes during the development and differentiation of multiple human cell types.