Gene Structure and Regulatory Mechanism of Gene Expression
The genomes of higher eukaryote are much bigger than those of bacteria. It is estimated that the human haploid genome is composed of about 3 × 109 nucleotides with a total length of 1,000 mm, and that only 10% of it is utilized as coding and regulatory sequences. The largest elucidated gene in a human chromosome contains as many as 2 × 106 nucleotides pairs (dystrophin gene, the gene for Duchenne and Becker muscular dystrophy diseases), and genes of more than 100,000 nucleotides pairs in length are not unusual . Assuming that a gene is 3–6 × 104 nucleotides in length, which includes the coding region and the non-coding and flanking sequences, this estimate would predict that there are about 5–10 × 104 human genes coding for different proteins (Table 1). To date, more than 1,600 human genes have been mapped to specific sites on 24 different nuclear chromosomes . Thus, the number of genes mapped corresponds to approximately 3% of all human genes in a haploid genome. The extrachromosomal 54 loci have been mapped on the mitochondrial DNA. Many genes in human genomes belong to multigene families, which can be either dispersed in different chromosomes or clustered into a single or tandemly repeated array. Intensive studies have indicated that genomic organization, gene structure, gene expression, and its regulation in eukaryotic cell would be more complex than that in prokaryotes, and have shown that higher eukaryote genomes have some unexpected features: interrupted structure, pseudogenes which are an inactive but stable component of the genome derived by mutation of an ancestral active gene, and genome rearrangement which occurs during B- and T-lymphoid cell differentiation. In this article, I describe the regulatory mechanism of eukaryotic gene expression with special reference to the transcriptional regulatory sequences (cis-elements) on a gene, general and tissue- specific transcription factors, and their interaction in activating gene expression.
KeywordsResponsive Element Zinc Finger Motif Growth Hormone Gene Universal Activator Eukaryotic Gene Expression
Unable to display preview. Download preview PDF.
- 1.Alberts B, Bray D, Lewis J, Raff M, Roberts K, Watson JD (1989) Molecular biology of the cell, 2nd edn. Garland, New YorkGoogle Scholar
- 2.Human Gene Mapping 10 (1989) 10th International Workshop on Human Gene Mapping. New Haven Conference. Cytogenet Cell Genet 51Google Scholar
- 3.Watson JD, Hopkins NH, Roberts JW, Steitz JA, Weiner AM (1987) Molecular biology of the gene, 4th edn. Benjamin/Cummings, Menlo Park, CaliforniaGoogle Scholar
- 4.Lewin B (1990) Gene I V. Oxford University Press, OxfordGoogle Scholar
- 10.Savagner P, Miyashita T, Yamada Y (1990) Two silencers regulate the tissue- specific expression of the collagen II gene. J Biol Chem 266: 6669–6674Google Scholar
- 14.Pugh BF, Tjian R (1990) Mechanism of transcriptional activation by Spl: Evidence for coactivators. Cell 61: 1187–1197Google Scholar
- 19.Evans T, Felsenfeld G (1989) The erythroid-specific transcription factor Eryfl: A new finger protein. Cell 58: 877–885Google Scholar
- 22.Herr W, Sturm RA, Clerc RG, Covcoran LM, Baltimore D, Sharp PA, Ingrahm HA, Rosenfeld MG, Finnay M, Rubkun G, Horvitz HR (1988) The POU domain: A large conserved region in the mammalian pit-1, oct-1, oct-2, and Caenorgabditis elegans unc-86 gene products. Genes Dev 2: 1513–1516PubMedCrossRefGoogle Scholar
- 24.Landschulz WH, Johnson PF, McKnight SL (1988) The leucine zipper: A hypothetical structure common to a new class of DNA binding proteins. Science 240: 1759–1764Google Scholar
- 29.Berger SL, Cress WD, Cress A, Triezenberg SJ, Guarente L (1990) Selective inhibition of activated but not basal transcription by the acidic activation domain of VP16: Evidence for transcriptional adaptors. Cell 61: 1199–1208Google Scholar
- 33.Lewis J, Martin P (1989) Limbs: A pattern emerges. Nature 342: 734–735Google Scholar