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23NEWGene Regulation in Eukaryotes

23NEWGene Regulation in Eukaryotes - Protein-protein...

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4 Protein-protein interactions (Figure 15.5b). An example is the formation of homodimers and heterodimers. Covalent modification of the transcription factor (Figure 15.5c). An example is the addition of a phosphate group. Steroid hormones exert their effects by binding to regulatory transcription factors. Regulatory transcription factors that interact with steroid hormones are called steroid receptors. Steroid hormones are designed to influence gene expression. Steroid hormones are synthesized by endocrine glands (mammals). The action of a glucocorticoid receptor is illustrated in Figure 15.6. Binding of the hormone to the glucocorticoid receptor releases a protein called HSP90, exposing a nuclear localization signal (NLS). Two glucocoricoid receptors form a dimer and bind to glucocorticoid response elements (GREs) in the nucleus. This activates the transcription of adjacent target genes. The CREB protein is an example of a regulatory transcription factor modulated by covalent modification. Most signaling molecules bind to receptors on the plasma membrane. This generates an intracellular signal, causing a cellular response. One of these responses may be transcription. The cAMP response-element binding protein (CREB) is an example (Figure 15.7). CREB proteins are regulatory transcription factors that become activated in response to cyclic-adenosine monophosphate (cAMP). The response element is called a cAMP response element (CRE). Changes in Chromatin Structure General information Alterations in DNA structure can affect gene expression by a variety of mechanisms (Table 15.1). Chromatin compaction. Tightly packed chromatin is said to be in the closed configuration. Chromatin in the open configuration is more accessible to transcription factors and RNA polymerase.
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5 Gene amplification increases the total copies of genes (uncommon). Gene rearrangement is used to produce a variety of similar proteins, as is the case with antibody production. DNA methylation may regulate genes in a tissue-specific manner. Gene accessibility can be controlled by changes in chromatin compaction. Variations in chromatin packing occur along the length of the chromosome during interphase. Tightly packed chromatin can’t be transcribed. The open complex must be packed into a structure that is less tightly packed than the 30 nm complex of chromatin organization. Figure 15.8 illustrates lampbrush chromosomes, the loops of which are open complexes that are actively being transcribed. Experiment 15A. DNase I sensitivity can be used to study changes in chromatin compaction. DNase I is an endonuclease that cleaves DNA. Accessible DNA is cut with DNase I, while inaccessible DNA is not. DNA that is accessible and has been digested with DNase I is too short to hybridize to a probe.
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