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Regulation of gene expression

Regulation of gene expression. Life of individual cells Cell cycle Pathogens during infection ( Shigella, EIEC) Environmental conditions (nutrients, toxic comp.) Multicellular organisms Cell differentiation (individual development) Environmental conditions (nutrients, hormones)

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Regulation of gene expression

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  1. Regulation of gene expression Life of individual cells Cell cycle Pathogens during infection (Shigella, EIEC) Environmental conditions (nutrients, toxic comp.) Multicellular organisms Cell differentiation (individual development) Environmental conditions (nutrients, hormones) Genetic diseases, cancer

  2. Gene expression must be regulated in time

  3. Gene expression must be regulated in space

  4. Gene expression must be quantitatively regulated

  5. What happens when gene regulation goes awry? • Developmental abnormalities (birth defects) Down Syndrome

  6. Regulation of gene expression DNA methylation, epigenetic changes Transcriptional regulation MicroRNAs (miRNAs), stability of mRNA, RNA processing Translational control Post-translational control

  7. Epigenetic regulation

  8. Methyl cytosine binding protein 2 The leading cause of RTT is sporadic mutations in a gene called MECP2, located on the X chromosome. Studies have shown that more then 95% of mutations originate from a mutated sperm. The MECP2 gene makes a protein, also called MeCP2, believed to play a pivotal role in silencing other genes. Scientists suspect that the inability to shut down specific genes causes the cascade of symptoms seen in RTT.

  9. Regulation of trp transcription Low tryptophane level – transcription of trp genes

  10. Synthesis of LacZYA proteins: 1. Glucose level - low glucose – high cAMP 2. Lactose level - high lactose transcription - High glucose – low cAMP Low lactose Low glucose – high cAMP Low lactose - + Low glucose – high cAMP High lactose High glucose – low cAMP High lactose -

  11. Regulation of lac transcription High glucose – low cAMP Low lactose Low glucose – high cAMP Low lactose CAMP receptor protein Low glucose – high cAMP High lactose High glucose – low cAMP High lactose b-galactosidase permease transacetylase

  12. Regulation of lac transcription

  13. Regulation of lac transcription CRP protein Lac repressor

  14. Regulation by attenuation

  15. Regulation of lac transcription

  16. DNA microarrays – regulatory gene identifications

  17. Differences in Genetic Organizationof Prokaryotes and Eukaryotes Monocistronic vs. polycistronic mRNA DNA binding proteins (histons & other) Repetitive sequences More than 95% DNA is untranslated Rearrangement of some genes (amplification, Ab, T-cells, methylation) Exons and introns Separated nucleus (transport of mRNA)

  18. Regulation of eukaryotic transcription

  19. Regulation of eukaryotic transcription

  20. Regulation of eukaryotic transcription

  21. MicroRNAs (miRNAs) are small, RNA molecules encoded in the genomes of plants and animals (Figure 1). These highly conserved, ~21-mer RNAs regulate the expression of genes by binding to the 3'-untranslated regions (3'-UTR) of specific mRNAs.Although the first published description of an miRNA appeared ten years ago (Lee 1993), only in the last two to three years has the breadth and diversity of this class of small, regulatory RNAs been appreciated. A great deal of effort has gone into understanding how, when, and where miRNAs are produced and function in cells, tissues, and organisms. Each miRNA is thought to regulate multiple genes, and since hundreds of miRNA genes are predicted to be present in higher eukaryotes (Lim 2003b) the potential regulatory circuitry afforded by miRNA is enormous. Several research groups have provided evidence that miRNAs may act as key regulators of processes as diverse as early development (Reinhart 2000), cell proliferation and cell death (Brennecke 2003), apoptosis and fat metabolism (Xu 2003), and cell differentiation (Dostie 2003, Chen 2003). Recent studies of miRNA expression implicate miRNAs in brain development (Krichevsky 2003), chronic lymphocytic leukemia (Calin 2002), colonic adenocarcinoma (Michael 2003), Burkitt’s Lymphoma (Metzler 2004), and viral infection (Pfeffer 2004) suggesting possible links between miRNAs and viral disease, neurodevelopment, and cancer. There is speculation that in higher eukaryotes, the role of miRNAs in regulating gene expression could be as important as that of transcription factors. Figure 1. Transcription of miRNAs. Approximately 60% of miRNAs are expressed independently, 15% of miRNAs are expressed in clusters, and 25% are in introns.

  22. miRNA Processing and Activity Mode of Action of miRNAs in Plants and Animals

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