The Initiator Element: A Paradigm for Core Promoter Heterogeneity within Metazoan Protein-coding Genes

In metazoans, an enormous number of protein-codinggenes must be differentially expressed in specific celltypes, during developmental processes, and in response toan array of extracellular signals. Combinatorial gene regulation strategies must be employed to generate these diverse expression patterns because only a limited number oftranscription factors can be encoded by a genome of limited size. Combinatorial regulation involves multiple layers of events: For a gene to be activated, higher-order chromatin structures must first be unpacked, individualnucleosomes must be remodeled, transcription factorsmust bind to promoters and enhancers, and the transcription factors must then communicate with the general transcription machinery in concert with appropriate coactivator proteins. Another fundamental feature of combinatorialregulation is the requirement for several distinct transcription factors to activate a gene. By combining each transcription factor encoded by the genome with various combinations of other factors, the number of gene expressionpatterns that can be achieved in an animal is greatly enhanced...