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Control of Eukaryotic
Gene Expression
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Eukaryotic Gene Regulation
Prokaryotic regulation is different from eukaryotic regulation.
1. Eukaryotic cells have many more genes (23,700 in human cells) in their genomes than prokaryotic cells (average 3000).
2. Physically there are more obstacles as eukaryotic chromatin is wrapped around histone proteins.
3. There are more non-histone proteins that are used in eukaryotic gene expression than in prokaryotic gene expression.
Eukaryotic Gene Regulation in Multicellular Organisms
• Almost all the cells in an organism are genetically identical or totipotent.
• Differences between cell types result from differential gene expression -- the expression of different genes by cells with the same genome.
• Errors in gene expression can lead to diseases including cancer.
• Gene expression is regulated at many stages.
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Types of Repetitive DNA
Altering the Genome is a Form of Gene Regulation
• Gene Loss-In gall midges (an insect) during development, all but two cells lose 32 of their 40 chromosomes during the first mitotic divisions. These cells that retain 40 chromosomes will produce gametes.
• Transposed genes-The hemoglobin gene has been duplicated, mutated, and transposed to other chromosomes to produce multiple but different copies of the same gene.
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• Gene amplification- In amphibian ovum there are over 1 million copies of the rRNA made from tiny circles of DNA in the nucleoli.
Gene Duplication and Transposition Regulates Genes
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• B lymphocytes can produce millions of different types of antibodies (proteins) that react with millions of different antigens. This happens by rearrangement of AB genes.
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Rearrangement Gene Domains Regulates Genes
Epigenetics
• Epigenetics refers to processes that influence gene expression or function without changing the underlying DNA sequence.
1. Acetylation
2. Methylation
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Acetylation• Acetylation of lysine found on the histone decreases the
affinity of histones for DNA and other histones, thereby making DNA more accessible for transcription.
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Methylation
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• A methyl group can be added to the nitrogenous bases of cytosine that are followed by guanine. Many human genes have upstream CG-rich regions called CpG islands. Methylation of a gene's CpG island represses gene expression. Different cells have different methylation patterns, which contributes to the differences in gene expression in different cell types.
Role of Transcription Factors
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Role of Transcription Factors
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Role of Transcription Factors and Activators
• This illustrates how different cells have different activators which activate different genes.
• The liver cells need the protein albumin and not the protein crystallin and the lens cells do not need albumin but do need crystallin.
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Role of Transcription Factors and Lactose Persistence
• The LCT gene produces the enzyme lactase which digests lactose. Lactose is a disaccharide found in dairy products. In order to be transcribed, the LCT gene needs a regulatory protein coded for by the MCM6 gene. Most humans after weaning cease to produce the regulatory protein but a mutation in the gene will allow its continued production through adulthood. This mutation causes a condition called lactose persistence.
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Coordination of Expression of Related Proteins in a Biochemical Pathway
Post-Transcriptional Control Alternative Splicing
Alternative splicing
• Once the immature mRNA is made, it could be processed in different ways to give rise to different mature mRNA and thus different proteins.
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Example of Alternative Splicing the Same Gene in Humans
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Post-Transcriptional Control and RNAiAlternative
• mRNA molecules do not remain functional indefinitely. This length of time can affect the number of protein product synthesize.
• Small pieces of RNA can interfere (RNAi) with mRNA by being complementary to a small part of the mRNA and tagging it for destruction.
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Post-Transcriptional Control and microRNA (miRNA)
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Post-transcriptional control- siRNA
Other Factors that Can Affect the Expression of Genes-Post Transcription
• Chemical signals that regulate the mRNA leaving the nucleus. Nearly half of all mature mRNA never reaches the cytoplasm. There must be some sort of inhibitor that will allow certain mRNA to leave and others toremain.
• Degrading of the mRNA that affects its lifespan. The life-span can be associated with the length of the poly-A-tail. As it shortens, it aids other enzymes with the removal of the 5'cap and nucleases break down the mRNA. mRNA can last from minutes to weeks.
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Post-translational control- Ubiquitin
Other Factors that Can Affect the Expression of Genes- Post Translation
Post-translational control
• Modification of protein product. Often amino acids must be removed in order for the protein to be functional.
• Proteins are often modified with prosthetic groups to make them functional.
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