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8/9/2019 7 Gene Expression
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Gene expression
1. Gene expression in prokaryotes2. Gene expression in eukaryotes
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Gene expression in prokaryotes
• Gene expression .•
gene expression .
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Development http://
1drv.ms/1wCyky2
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Cell differentiation4
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Gene expression• All somatic cells : genetically identical• Cells differentiate : gene expression
http://
1drv.ms/1wCEXjQ
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Cell signaling• Proliferation/apoptosis• Differentiation• Protein secretion• Migration
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Cell signaling• Receptor
– Extracelluar, intracellular receptor
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Cancer : loss of regulatory controls
http:// 1drv.ms/18wUWvx
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Prokaryotic gene expression• Rapid, reversable response to environment• Operon : unit of gene regulation
– Cluster (genes + DNA sequences for regulation) – Promoter : RNA polymerase binding – Transcriptional unit – Operator : repressor, activator
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lac Operon• Lactose metabolism in E. Coli• 3 genes (lacZ, lacY and lacA) : lactose ,• Promoter, operator, repressor• Inducer
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http:// 1drv.ms/1wCHVVDhttp:// 1drv.ms/1wCI4YZ
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trp Operon• Tryptophan : amino acid• 5 genes (trpA ~ trpE) : synthesis of tryptophan• Promoter, operator, repressor• Corepressor
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Gene expression in eukaryotes
• .
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Regulation of gene expression• Main control
– Transcriptional regulation• Additional controls
– Posttranscriptional regulation – Translational regulation – Posttranslational regulation
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Transcriptional regulation• Chromatin remodeling• Transcription initiation
regulation – Transcription complex – Activators, coactivators,
enhancer, repressors – Combinatorial gene
regulation – Hormones
• DNA Methylation
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Chromatin remodeling• Chromatin structure
– Eukaryotic DNA – Nucleosomes, histones
http:// 1drv.ms/1y80QcB
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Chromatin remodeling• Promoter• Activator• Remodeling complex
http:// 1drv.ms/1CgzCHd
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Transcription initiation regulation• Eukaryotic gene organization
– Promoter : TATA box, transcription factors binding – Promoter proximal region – Enhancer
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Transcription initiation regulation• Transcription complex on the promoter
– General transcription factors : TATA box – RNA polymerase II
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Transcription initiation regulation• Activators
– Promoter proximalelements
– Transcription rate ↑• Coactivators
–
Enhancerpromoter• Enhancer
– Maximuntranscription rate
• Repressors – Opposite effect of
activator
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Transcription initiation regulation• Combinatorial gene regulation
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Transcription initiation regulation• Hormones
– Steroid hormone – Ex) sex hormone, – gene
transcription –
hormone receptors
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Methylation of DNA• CH3 to cytosine
– Gene silencing – Example: hemoglobin
• Genomic imprinting – Permanent silencing of a maternal
or paternal allele
http:// 1drv.ms/1Bs4cIo
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Posttranscriptional regulation• Alternative splicing• Masking proteins• mRNA breakdown rate
– Casein : peptide hormone – 5’ UTR nucleotide sequences
• RNA interferance (RNAi) – Micro-RNA (miRNA) – Small interfering RNA (siRNA)
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Alternative splicing28
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RNA interference (RNAi)29
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Translational regulation• Length of poly(A) tail
– Translation ↑
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Posttranslational regulation• Chemical modification• Protein processes• Protein degradation
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Posttranslational regulation• Chemical modification
– Phosphate addition : proteinactivity ↑ or ↓
• Protein processes – Inactive precursers → active
proteins – Ex) pepsinogen → pepsin,
proinsulin → insulin• Rate of degradation
– Ex) ubiquitin
