Core promoters: active contributors to combinatorial gene regulation
- Howard Hughes Medical Institute, Department of Microbiology, Immunology, and Molecular Genetics, and Molecular Biology Institute, University of California, Los Angeles, California 90095-1662, USA
This extract was created in the absence of an abstract.
In metazoans, thousands of protein-coding genes must be differentially expressed in specific cell types, during development, and in response to a wide variety of extracellular signals. Combinatorial gene regulation strategies are required to generate these diverse expression patterns because only a limited number of transcription factors can be encoded by a limited genome. For a gene to be activated, transcription factors must bind distant control regions and promote the decondensation of repressed chromatin. Then, factors bound to distant control regions and the promoter must stimulate the remodeling of individual nucleosomes and transcription initiation by RNA polymerase II, via effective communication with nucleosome remodeling complexes, coactivator complexes, and the general transcription machinery (Lemon and Tjian 2000). Another important feature of combinatorial regulation is the requirement for several distinct transcription factors to activate a gene (Merika and Thanos 2001). By employing combinations of factors, the number of gene expression patterns that can be achieved is greatly enhanced.
Although combinatorial regulation has been widely studied, one potential contributor has received relatively little attention: the core promoter, which is located between approximately −35 and +35 relative to the transcription start of a metazoan gene. One reason the core promoter generally was not considered to be an active contributor to combinatorial regulation is historical; when the first protein-coding genes were isolated, virtually every gene, regardless of its expression pattern, contained an A/T-rich sequence 25–30 base pairs (bp) upstream of the transcription start site (Breathnach and Chambon 1981). This sequence, with the consensus TATAAA, was called the TATA box. Following the development of functional assays, mutations in TATA boxes were found to reduce transcription initiation and prevent the proper positioning of transcription start sites. Based on these early observations, it was expected that a similar core promoter structure would be found in every cellular gene. The …
