Lecture19S10

Lecture19S10 - BIS101/Engebrecht Lecture19 5/13/10 Control...

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BIS101/Engebrecht Lecture19 5/13/10 Control of gene expression in eukaryotes The biggest difference between a prokaryotic and eukaryotic cell is that the latter is compartmentalized. Instead of transcription and translation being coupled as in prokaryotic cells, in eukaryotes transcription occurs in the nucleus and the processed mRNA is then transported to the cytoplasm, where translation takes place. This compartmentalization offers new regulatory avenues for the cell to control its response to its environment. There are four main levels of control for regulating gene expression available to the eukaryotic cell: 1) DNA level 2) Transcription initiation level 3) RNA level 4) Protein level DNA level: The size of the genome dramatically increases without a corresponding increase in the number of genes. Because of the large size, compaction of the DNA is necessary (for chromosome segregation, as we saw previously) but that means that there must be mechanisms to relieve the compaction for the transcriptional machinery to have access to the DNA. The DNA compaction state is regulated by both cis-acting sequences (on the DNA molecules themselves) and trans-acting factors (proteins). Regions of the genome that contain a number of CpG dinucleotides (cis-acting sequences) tend to be repressed (and compacted) because the C becomes methylated. Highly methylated CpG islands (regions of DNA) correlate with transcriptional repression. Mechanistically, this is mediated, at least in part, by the binding of a protein (trans acting factor) to the methylated CpGs. Not all eukaryotes use CpG methylation as means to alter the transcriptional state – this is found in mammals but not lower eukaryotes like yeast. Furthermore, in cancer cells and aging, methylation patterns change suggesting that this may be important in both turning on and off genes in the pathogenesis of cancer (and perhaps aging). Another important target at the DNA level, is the histones. We saw previously that histones make up nucleosomes, the first level of compaction of the chromosome. Histones can be post-translationally modified by acetylation (as well as methylation and phosphorylation). In general, high levels of acetylation correlate with active transcription, while low levels correlate with regions of the genome that are repressed (keep in mind that all of the many histone modifications are integrated and coded and it may not be quite so simple as I presented it). Histone acetylase and deacetylases (enzymes that add and remove acetyl groups, respectively) turn out to be co-activators and co-repressors, thus directly influencing transcription. The last trans-acting factor I told you about was DNA-dependent ATPases. These enzymes bind DNA, hydrolyze ATP (for energy) and thereby modify the interaction between the nucleosomal histones and the DNA. This results in a “loosening up” of the chromatin, making it more accessible for the transcriptional machinery. Summary:
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This note was uploaded on 07/02/2010 for the course BIS 101 taught by Professor Simonchan during the Spring '08 term at UC Davis.

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Lecture19S10 - BIS101/Engebrecht Lecture19 5/13/10 Control...

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