Control of gene expression

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Control of gene expression

• Transcriptional
• Post-transcriptional
• Epigenetics and long range control

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Control of gene expression

• Transcriptional
• Tissue specific transcription factors
• Binding of hormones, growth factors etc. to
  response elements
• Use of alternative promoters in a single gene

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Control of gene expression

• Post-transcriptional
• Alternative splicing
• Alternative polyadenylation
• Tissue specific RNA editing
• Translational control mechanisms

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Control of gene expression

• Epigenetics and chromatin structure
• Allelic exclusion (rearrangements, imprinting, X
  inactivation)
• Long range control by chromatin structure
  (position effects Pax6 in aniridia)
• Cell position-dependent, short range signaling

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Control of gene expression

• rRNA synthesis
• Arrows indicate cleavage sites

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Control of gene expression

• Initiation of transcription (RNA pol I)

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Control of gene expression

• tRNA and 5s RNA promoter elements
• Initiation of transcription (RNA pol III)

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Control of gene expression

• Conserved locations of promoter elements in
  eukaryotes

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Control of gene expression

• Insulin gene promoter organization
• NRE negative regulatory element
• CRE cAMP response element

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Control of gene expression

• HS-40 alpha-globin regulatory site
• Tissue specific regulation (many sites)

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Control of gene expression

• Structural domains in transcription factors
• HTH
• HLH
• Zn Finger
• Alpha-helix

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Control of gene expression

• Binding of conserved motifs to double helix

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Control of gene expression

• Steroid receptors and response elements
• GR
• ER
• PR
• RAR
• TR
• VDR

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Control of gene expression

• Transcription regulation by glucocorticoids

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Control of gene expression

• Target gene expression via signal transduction
• Protein kinase hormonal signaling through
  cAMP-pt kinase A pathway
• Cytoplasmic transcription factor NF kappa B and
  translocation to the nucleus

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Control of gene expression

• Major Classes of Cell Surface Receptor
• G protein coupled
• Serine-Threonine kinase
• Tyrosine kinase
• Tyrosine kinase associated JAK (janus protein
  kinase) activity in JAK-STAT signaling
• Ion channel-linked

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Control of gene expression

• Secondary Messengers in Cell Signaling
• Cyclic AMP (cAMP)
• Cyclic GMP (cGMP)
• Phospholipids/Ca

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Control of gene expression

• The IRE binding protein and iron-response
  elements (IREs)

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Control of gene expression

• Genes with multiple promoters
• Dystrophin has eight promoters

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Control of gene expression

• Differential RNA splicing
• Wt1 Wilms tumor (four splice forms)
• Calcitonin gene (tissue specific products)

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Control of gene expression

• Tissue specific RNA editing
• Apolipoprotein B gene (rare)

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Control of gene expression

• Methylation and gene expression
• Largely confined to CpG dinucleotides
• CpG islands
• Methylation patterns change during development
• Sex-specific regulation

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Control of gene expression

• Methylation
• CpG islands

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Control of gene expression

• Methylation
• Changes in methylation throughout development

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Control of gene expression

• Methylation
• Sex-specific regulation of the Dnmt1 methyl
  transferase gene
• 1so somatic
• 1sp spermatocytes
• 1oo oocytes

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Control of gene expression

• Transcriptional repression by histone
  deacetylation
• Mediated by methylation
• Methylated CpGs bound by MeCP2 repressor

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Control of gene expression

• Gene clusters
• Coordinated switching
• Locus control region
• Globin genes

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Control of gene expression

• Imprinting
• DNA methylation key component
• Selective expression of genes
• Nonequivalence of maternal and paternal genomes

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Control of gene expression

• Monoallelic expression from biallelic genes
• Allelic exclusion according to parent of origin
• Genomic imprinting
• Allelic exclusion independent of parent of origin
• X-chromosome inactivation
• Programmed DNA rearrangement
• Unknown mechanism

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Control of gene expression

• Programmed rearrangement
• Ig and TCR loci in B and T lymphocytes

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Control of gene expression

• Programmed rearrangement
• Ig heavy chain locus on 14q32
• 86 variable (V) sequences
• 30 diversity (D) sequences
• 9 joining (J) segments
• 11 constant (C) sequences

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Control of gene expression

• Programmed rearrangement
• Light chain synthesis
• Somatic recombination V to J
• RNA splicing VJ to C
• Heavy chain synthesis
• Two sequential somatic recombination events yield
  DJ and VDJ
• RNA splicing VDJ to C
• Somatic recombination VDJ to different C
  (switching)

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Control of gene expression

• Inversion or deletion based splicing
• Ig kappa light chain
• V-J splicing

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