Gene expression DNA أ†RNA أ†Protein - Queen's biol330/Chapter 7 new.pdfآ  Gene expression ....

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Transcript of Gene expression DNA أ†RNA أ†Protein - Queen's biol330/Chapter 7 new.pdfآ  Gene expression ....

  • Gene expression DNA RNA Protein

    DNA

    DNA

    RNA

    Protein

    Replication

    Transcription

    Translation

    Degradation

    Degradation

    Initiation Elongation Processing Export

    Initiation Elongation Processing Targeting

  • Chapter 7: Gene control

    Control of gene expression is critical in mediating cellular changes:

    •Executing developmental programs •Controlling cell cycle •Responsiveness to regulators

    There are many examples of evolutionary variation in promoters and transcriptional regulators

  • Since all cells in an organism have the same DNA, how do the cells become different?

    (1) Some genes are expressed only in specific tissues (e.g., hemoglobin)

  • Since all cells in an organism have the same DNA, how do the cells become different?

    (2) Genes expressed in all cells are termed housekeeping genes: • cytoskeleton building blocks • metabolism • histones, polymerases

  • Since all cells in an organism have the same DNA, how do the cells become different?

    (3) Even housekeeping genes are expressed at different levels -metabolic profiles of red and white muscle

  • Since all cells in an organism have the same DNA, how do the cells become different?

    (4) Post-transcriptional processes (Fig 7-5) also critical in regulating function: -mRNA processing -mRNA transport and localization -mRNA degradation -translation -post-translational modification -3-dimensional organization -compartmentation -protein degradation

  • Fig 7-5. Gene expression is controlled at many levels

  • Cells can change expression in response to external signals

    Many cells use hormonal signals to trigger changes in gene expression:

    e.g., glucocorticoids induce changes in metabolic enzyme expression in liver

  • Cells can change expression in response to external signals

    Different cells respond differently to the same hormones:

    e.g., glucocorticoids in liver: induction of genes that enhance conversion of amino acids to glucose.

    -in adipocytes, glucocorticoids repress the same gene

  • Transcriptional control

    Genes are regulated by promoters (regions upstream of coding region)

    Genes can also be regulated at sites that are distant from promoters (even in introns)

  • Gene regulatory proteins

    Regulatory regions of DNA have short sequences (elements) that bind specific gene regulatory proteins

    e.g., Sp1 binds GGGCGG CCCGCC

    These proteins recognize subtle differences in the structure of the outside of the major groove of the DNA double helix

  • Gene regulatory proteins

    Each protein differs in how it binds DNA and how it interacts with other proteins

    Several common DNA binding motifs including:

  • -helix-turn-helix motif (Fig 7-14), include homeodomain proteins

  • -zinc finger proteins (Figs 7-17-19)

  • -leucine zippers (Fig. 7-21)

  • -helix-loop-helix (HLH) (Fig 7-25)

  • Gene regulatory proteins

    DNA binding ability of gene regulatory proteins can be influenced by:

    -localization

    -dimerization (homodimers vs heterodimers)

  • Tryptophan repressor is a simple model of ligand-dependent gene regulation

    (Fig-7-34, 7-35)

    Repressor protein can bind DNA and trp

    If trp absent, repressor cannot bind DNA (un- repressed)

    When trp available, repressor binds and prevents RNA Pol from binding gene

  • Eukaryotic gene expression What regulates transcription (Fig 7-41)

    Promoter: binding site for RNA Pol II and general transcription factors

    Other regulatory sequences can be far away (even 50,000 bp)

    Activators (or enhancers) bind to specific DNA sequences (modify local DNA structure)

  • Eukaryotic gene expression

  • Gene activators

    Activators can work synergistically (Fig 7-47)

    Order of binding of activators and combination of activators influences transcription (Fig 7-48)

  • Gene repressors

    Repressors can work many different ways (Fig 7-49)

    -competition with activators for sites

    -masking activation site on activator

    -disruption of general transcription factors

    -affecting chromatin remodelling

  • Co-activators and co-repressors

    These proteins do not bind DNA but bind DNA- binding proteins (Fig 7-50)

  • Myogenesis: an example of programmed transcriptional regulation (Fig 7-72)

    Precursor cells are myoblasts

    Hormonal conditions cause differentiation: turning on suites of muscle-specific genes in the appropriate order

    Hormones induce expression of myogenic factors (transcription factors)

  • Control of gene expression 1. Localization of transcription factors

    X kinase

    kinase

    Hormone

  • Control of gene expression 2. Dimerization

    kinase

    kinase

    Hormone

  • Control of gene expression 3. Affinity for DNA (phosphorylation dependent)

    kinase

    kinase

    Hormone

  • Control of gene expression 4. Affinity for DNA (ligand dependent)

    Hormone

  • Control of gene expression 5. Affinity for DNA (ligand dependent)

    Hormone

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