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Signal NUCLEUS Chromatin Gene regulation in Eukaryotes Chromatin modification: DNA Today’s topics: • Control of transcription Gene RNA – Combinatorial control – Cell-specific transcription Transcription Exon Intron RNA processing • Chromatin remodeling • Post transcription gene regulation Transport to cytoplasm Degradation of mRNA – mRNA processing – Micro RNAs – Protein degradation CYTOPLASM Translation Polypetide 28 November 2012 Chemical modification Transport to cellular destination Active protein Degradation of protein Degraded protein Control of Transcription in Eukaryotes Transcriptional synergy • Combinations of different enhancers affect the strength of transcription Promoter Activators DNA Enhancer Distal control element Activator proteins bind to enhancer sequences Gene Repressor proteins can inhibit transcription TATA box General transcription factors compete for binding site DNA-bending protein Group of mediator proteins “hide” activator RNA polymerase II Now transcription can start RNA polymerase II Transcription initiation complex interact with transcription factors at the promoter RNA synthesis Fig. 18-9 1 Enhancer Promoter All cells have the same genes, but only certain genes are expressed in each tissue Albumin gene Crystallin gene GFP gene attached to cartilage-specific control elements Albumin gene not expressed Albumin gene expressed Liver cell Different activator proteins in the two cell types Lens cell Crystallin gene not expressed Crystallin gene expressed Fig. 18-10 Signal NUCLEUS Chromatin Nucleosomes Chromatin modification DNA Gene available for transcription Gene Transcription RNA Exon Primary transcript Intron RNA processing Tail Cap mRNA in nucleus Transport to cytoplasm CYTOPLASM Fig. 18-6 Histone acetylation loosens DNA to allow transcription Unacetylated histones Long-term control of transcription: methylation Acetylated histones positive charge (interacts with DNA) acetylation neutralizes charge Acetyl group Lysine 2 Signal Alternative RNA splicing NUCLEUS Chromatin modification: DNA Chromatin changes Transcription Gene Transcription RNA processing RNA Posttranscription control of gene expression mRNA degradation RNA processing Translation Protein processing and degradation Transport to cytoplasm CYTOPLASM Degradation of mRNA Exons DNA Translation Polypetide Primary RNA transcript Activation Active protein RNA splicing Degradation of protein Degraded protein or mRNA CYTOPLASM Protein-coding RNA only accounts for ~1.5% of the human genome, but ~90% of the genome appears to be transcribed… What is it?? mRNA in cytoplasm Degradation of mRNA Translation Polypeptide Protein activation Degradation Degradation of protein of protein -rRNAs -tRNAs -snRNAs -small regulatory RNAs Active protein Transport to cellular destination Cellular function Fig. 18-6 Hairpin miRNA and developmental complexity miRNA Hydrogen bond Dicer miRNA 5! 3! (a) Primary miRNA transcript microRNAs (miRNAs) Technau 2008 Nature 455:1184 mRNA degraded miRNAprotein complex Translation blocked Fig. 18-13 3