| BASIC MECHANISMS OF GENE EXPRESSION
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| Gene expression encompasses several different processes
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| The control of human gene expression occurs principally at the level of transcription. However, transcription is just one step in the conversion of the genetic information encoded by a gene into the final processed gene product, and it has become increasingly clear that post-transcription events occur that may also have an important role in regulating the expression of a gene. The sequence of events involved may be summarized as:
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initiation of transcription
- → processing the transcript
- → transport to cytoplasm
- → translation of transcript to protein
- → posttranslational processing of the protein
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| Gene expression in humans can be regulated in many ways, both at specific phases in development and in differentiated tissues of mature organisms. Clearly, during the growth of a human embryo from a single fertilized ovum to a newborn infant, there must be numerous changes in the regulation of genes, to allow the differentiation of a single cell into many types of cells that develop tissue-specific characteristics. Similarly, at puberty there are changes in the secretion of pituitary hormones that result in the cyclic secretion of ovarian and adrenal hormones in females and the production of secondary sexual characteristics. Such programmed events are common in all cellular organisms, and the production of these phenotypic changes in cells - and thus the whole organism - arises as a result of changes in the expression of key genes. These key genes vary from cell to cell and also in time, but the mechanisms underlying the changes in regulation are less variable. In humans and other eukaryotes, mechanisms that regulate transcription (Table 33.1) are manifold, as are the factors that influence them.
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| Gene transcription requires key elements to be present in the region of the gene
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Table 33-1.
Mechanisms involved in the regulation of gene expression in humans. |
| Body_ID: None |
| Regulation of gene expression |
| Body_ID: T033001.50 |
| Mechanism | Example |
| Body_ID: T033001.100 |
| Transcriptional level |
| Body_ID: T033001.150 |
| transcription by tissue-specific factors | muscle-cell-specific transporter factor (MyoD): in myoblasts |
| Body_ID: T033001.200 |
| | Ker 1 =keratinocyle differentiation factor - skin cells |
| Body_ID: T033001.250 |
| | HNF-5 =hepatic nuclear factor-5 - liver cells |
| Body_ID: T033001.300 |
| | TATA box: binds transcription factor IID (TFIID) |
| Body_ID: T033001.350 |
| hormone, growth factor, or cellular messenger bindingto response element | glucocorticoid response element (GRE): binds glucocorticoid receptor complex |
| Body_ID: T033001.400 |
| alternative promoters | dystrophin gene |
| Body_ID: T033001.450 |
| Post-transcriptional level |
| Body_ID: T033001.500 |
| tissue-specific RNA processing | alternative splicing, e.g. immunoglobulin genes |
| Body_ID: T033001.550 |
| | alternative polyadenylation signals, e.g. calcitonin-related gene peptide |
| Body_ID: T033001.600 |
| RNA editing | editing of apoB mRNA |
| Body_ID: T033001.650 |
| RNA translation | ferritin and transferrin |
| Body_ID: T033001.700 |
| RNA stability | transferrin receptor, cyclooxygenase-2 |
| Body_ID: T033001.750 |
| The key step in the transcription of a protein-coding gene is the conversion of the information held within the DNA of the gene into messenger RNA, which can then be used as a
template for synthesis of the protein product of the gene. For expression of a gene to take place, the enzyme that catalyzes the formation of mRNA, RNA polymerase II (RNAPol II), must be able to recognize the so-called startpoint for transcription of the gene. RNAPol II uses one strand of the DNA template to create a new, complementary RNA (often called the primary transcript), which is then modified in various ways (commonly including addition of a methylated guanine nucleotide cap, addition of a polyA tail, and splicing out of introns) to form a mature mRNA (Chapter 31). However, RNAPol II cannot initiate transcription alone. This enzyme requires other factors to assist in recognition of critical gene sequences and other proteins in the vicinity of the start point for transcription.
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