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Medical and Molecular Genetics
Lecture 7 Regulation of Gene Expression
1) Define the terms cis-acting and trans-acting and give examples of cis-acting
elements and trans-acting factors responsible for gene regulation. Cis-acting
elements are the DNA sequences that participate in regulating genes. Trans-acting
factors are the proteins that interact with cis-acting elements. These elements and
factors working together serve to induce, repress, de-induce, or de-repress the
expression of a gene. There are two major types of cis-acting elements: promoters and
regulatory elements (response elements and enhancers). Trans-acting factors bind to
either cis-acting elements, other factors, or RNA polymerase.
2) Distinguish the differences between a promoter, a response element, and an
enhancer. Promoters are the sites where RNA polymerase must bind to the DNA in
order to initiate transcription. Response elements are DNA sequences that
coordinately regulate the expression of groups of genes and are located a few hundred
base pairs upstream of the promoter. Enhancers are basically the same as response
elements, but they differ from a regular response element in that they can function
either upstream, within, or downstream of a gene.
3) List the types of domains that a trans-acting factor may need for activity. Transacting factors may contain multiple domains required for activity: a DNA-binding
domain, a ligand-binding domain, phosphorylation sites, an oligomerization domain,
and a transcription-activating domain.
4) Diagram how steroid receptors regulate transcription. Steroid receptors function
as homodimers and bind to response elements that consist of inverted repeat
sequences separated by 3 base pairs. Inactive steroid receptors are bound to a dimeric
protein called hsp 90 in the cytoplasm. Upon binding of the steroid, the receptor
dissociates from the hsp 90. The hormone bound receptor is then transported into the
nucleus where it then binds as a homodimer to its target response element. The
receptor’s transcriptional activation domain interacts with the transcription machinery
and induces or represses transcription. Once concentration of the hormone drops, the
receptor dissociates and is no longer capable of binding the hormone. It must be
transported back to the cytosol and re-associate with hsp 90 before it can bind again.
5) Explain how alternative RNA processing and repression of translation affect
gene expression. Alternative RNA processing alters gene expression to achieve tissue
specific expression of certain proteins. Alternative polyadenylation sites and/or
alternative splice sites are frequencly used to generate similar proteins with specific
tissue functions. Repression of translation is accomplished through a sequence of the
Iron Responsive Element of the transferring receptor mRNA, which is also found in
the 5’ end of apoferritin mRNA. However, since it binds at the 5’ end it represses
translation of the apoferritin mRNA until high concentrations of iron bind the
repressor protein and induce it to dissociate from the mRNA.