Harpers

REGULATION OF GENE EXPRESSION / 395Other sequences in the 3′ ends of certain eukaryoticmRNAs appear to be involved in the destabilization ofthese molecules. Of particular interest are AU-rich regions,many of which contain the sequence AUUUA.This sequence appears in mRNAs that have a very shorthalf-life, including some encoding oncogene proteinsand cytokines. The importance of this region is underscoredby an experiment in which a sequence correspondingto the 3′ noncoding region of the short-halflifecolony-stimulating factor (CSF) mRNA, whichcontains the AUUUA motif, was added to the 3′ end ofthe β-globin mRNA. Instead of becoming very stable,this hybrid β-globin mRNA now had the short-half-lifecharacteristic of CSF mRNA.From the few examples cited, it is clear that a numberof mechanisms are used to regulate mRNA stability—justas several mechanisms are used to regulate thesynthesis of mRNA. Coordinate regulation of these twoprocesses confers on the cell remarkable adaptability.SUMMARY• The genetic constitutions of nearly all metazoan somaticcells are identical.• Phenotype (tissue or cell specificity) is dictated bydifferences in gene expression of this complement ofgenes.• Alterations in gene expression allow a cell to adapt toenvironmental changes.• Gene expression can be controlled at multiple levelsby changes in transcription, RNA processing, localization,and stability or utilization. Gene amplificationand rearrangements also influence gene expression.• Transcription controls operate at the level of protein-DNA and protein-protein interactions. These interactionsdisplay protein domain modularity and highspecificity.• Several different classes of DNA-binding domainshave been identified in transcription factors.• Chromatin modifications are important in eukaryotictranscription control.REFERENCESAlbright SR, Tjian R: TAFs revisited: more data reveal new twistsand confirm old ideas. Gene 2000;242:1.Bird AP, Wolffe AP: Methylation-induced repression—belts, bracesand chromatin. Cell 1999;99:451.Berger SL, Felsenfeld G: Chromatin goes global. Mol Cell 2001;8:263.Busby S, Ebright RH: Promoter structure, promoter recognition,and transcription activation in prokaryotes. Cell 1994;79:743.Busby S, Ebright RH: Transcription activation by catabolite activatorprotein (CAP). J Mol Biol 1999;293:199.Cowell IG: Repression versus activation in the control of gene transcription.Trends Biochem Sci 1994;1:38.Ebright RH: RNA polymerase: structural similarities between bacterialRNA polymerase and eukaryotic RNA polymerase II.J Mol Biol 2000;304:687.Fugman SD: RAG1 and RAG2 in V(D)J recombination and transposition.Immunol Res 2001;23:23.Jacob F, Monod J: Genetic regulatory mechanisms in protein synthesis.J Mol Biol 1961;3:318.Lemon B, Tjian R: Orchestrated response: a symphony of transcriptionfactors for gene control. Genes Dev 2000;14:2551.Letchman DS: Transcription factor mutations and disease. N EnglJ Med 1996;334:28.Merika M, Thanos D: Enhanceosomes. Curr Opin Genet Dev2001;11:205.Naar AM, Lemon BD, Tjian R: Transcriptional coactivator complexes.Annu Rev Biochem 2001;70:475.Narlikar GJ, Fan HY, Kingston RE: Cooperation between complexesthat regulate chromatin structure and transcription.Cell 2002;108:475.Oltz EM: Regulation of antigen receptor gene assembly in lymphocytes.Immunol Res 2001;23:121.Ptashne M: Control of gene transcription: an outline. Nat Med1997;3:1069.Ptashne M: A Genetic Switch, 2nd ed. Cell Press and Blackwell ScientificPublications, 1992.Sterner DE, Berger SL: Acetylation of histones and transcriptionrelatedfactors. Microbiol Mol Biol Rev 2000;64:435.Wu R, Bahl CP, Narang SA: Lactose operator-repressor interaction.Curr Top Cell Regul 1978;13:137.