Gene Expression• Different cell types from the same organism have the same genome.• Different cell types produce different sets of proteins accounting for differences in cell appearance and function.• Gene expression: process that results in the generation of a specific protein or RNA moleculeGene expression can be regulated at multiple steps.• The promoter binds the RNA polymerase and correctly orients the enzyme to begin its task of making an RNA copy of the gene • Regulatory DNA sequences are used to switch the gene on or off • Transcription regulators binds to regulatory DNA sequences and control gene transcriptionTranscriptional regulators bind to specific regulatory DNA sequences.Protein-DNA interactions are among the tightest and most specific Molecular Interactions known in biology• Transcriptional regulators generally recognize specific sequences in the DNA by binding to the edges of the bases Form hydrogen bonds, ionic bonds, and hydrophobic interactions with DNA Usually bind in the major groove of the DNA helix Does not disrupt the hydrogen bonds that hold the double helixA cluster of bacterial genes can be transcribed from a single promoter. These five genes are transcribed as a single mRNA molecule, a feature that allows their expression to be coordinatedIn bacteria, transcription regulators bind to regulatory DNA sequences close to where RNA polymerase bindsGenes can be switched off by repressor proteins.Genes can be switched on by activator proteinsThe Lac operon is controlled by two transcription regulators• In bacteria, transcription regulators usually bind to regulatory DNA sequences close to where RNA polymerase binds. This binding can either activate or repress transcription of the gene. • In eukaryotes, regulatory DNA sequences are often separated from the promoter by many thousands of nucleotide pairsEukaryotic transcription is regulated by transcriptional activators and repressors that act at a distance.Some transcriptional regulators recruit chromatin modifying proteins.1. Histone tail modifying enzymesa. histone acetyltransferase=promote txnb. histone deacetyltransferase=inhibit txn2. Chromatin modifying complexesEukaryotic transcription regulators• Eukaryotic transcription regulators act in two main ways. 1. They can directly affect the assembly process that require RNA polymerase and the general transcription factors at the promoter.2. They can locally modify the chromatin structure of promoter regions.Combinatorial control: multiple transcriptional regulators act to control the expression of a single geneA single transcriptional regulator can control the expression of many genes. The cortisol-responsive genes share a DNA sequence in their regulatory regions that binds the cortisol-responsive transcriptional activator.Cell memory allows a proliferating cell to transmit its cell identity to its daughter cells.1. Positive feedback: All of the descendants of the original cell will remember that the progenitor cell had experienced a transient signal that initiated the production of protein A2. Transmission of DNA methylation patterns: (inactive genes are methylated)DNA methylation patterns are passed on to progeny cells by the actionof an enzyme that copies the methylation pattern DNA strand to the daughter DNA strand as it is synthesized3. Inheritance of histone modifications:Epigenetic inheritance: transmission of the pattern of gene expression without modifying the DNA nucleotide sequence.An miRNA targets a complementary mRNA molecule for destruction. RISC:RNA- induced silencing complexsiRNAs are produced from double-stranded, foreign RNAs in the process of RNA interferencesiRNA: Small interfering RNA• MicroRNAs (miRNAs) control gene expression by base-pairing with specific mRNAs and inhibiting their stability and translation • Cells have a defense mechanism for destroying “foreign” double stranded RNAs, many of which are produced by viruses. It makes use of small interfering RNAs (siRNAs) that are produced from the foreign RNAs in a process called RNA interference
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