Differential Gene Expression

1
Differential Gene Expression

• Turning Genes on or keeping them off?

2
Differential Gene Regulation

• Transcriptional regulation
• Post-transcriptional regulation
• Translational regulation
• Post-translational regulation

3
Differential Gene Expression

• Transcriptional
• Post-transcriptional
• Translational
• Post-translational

• Transcription factor binding
• Transcription factor interactions
• Methylation
• Nucleosome/chromatin structure

4
Differential Gene Expression

• Splicing
• Polyadenylation
• Stability

• Transcriptional
• Post-transcriptional
• Translational
• Post-translational

5
Differential Gene Expression

• Masking
• Antisense RNA

• Transcriptional
• Post-transcriptional
• Translational
• Post-translational

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Differential Gene Expression

• Glycosylation
• Acylation
• Proteolytic processing

• Transcriptional
• Post-transcriptional
• Translational
• Post-translational

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Differential Gene Regulation

• Hierarchies of transcriptional regulatory
  proteins
• Transcription Factors
• Regulators of regulators

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Transcription Initiation
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Transcriptional Activation
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Transcription Control Elements

• Promoter
• Basal elements (sites)
• TATAA box
• CCAAT box
• GC boxes
• Orientation and position dependent
• Enhancer
• Any combination of transcription factor binding
  sites
• Orientation and position independent
• Silencer
• Binding site for proteins which make DNA
  inaccessible to txn factors

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Transcription Factors

• Basal/General Txn Factors
• TFIID
• TBP - TATA binding protein
• TAFs TBP associated factors
• CBP CCAAT binding protein
• SP1 GGCGGG binding protein
• Give a low level of txn
• Often found as the only txn control elements of
  housekeeping genes

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Transcription Factors

• Gene Specific Txn Factors
• Classified by DNA binding domains mechanism of
  transcriptional activation

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Transcription Factor Flavors
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Take A Look
www.devbio.com Website 5.4
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Physical Arrangement of Regulatory Elements
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Cell-Type Specific Transcription

• Tissue specificity
• Promoter
• Enhancer
• Tissue specific txn factor and cognizant DNA
  element (site)

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Epigenetic Gene Regulation
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Differential Gene Expression Via
Posttranscriptional Regulation
Alternative or Differential Splicing
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Differential Splicing

• Differential splicing requires cell-type specific
  splicing factors
• Often one spliced mRNA does not encode a
  functional protein
• When both alternative mRNAs encode functional
  proteins, one protein typically lacks an entire
  functional domain

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Differential Splicing
Sex Determination in Drosophila Regulated by
Differential Splicing
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Differential Splicing Sex
Boys
Girls
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(No Transcript)
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3 UTR Mediates Stability or Instability
U-Rich 3UTR mediates degradation of
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Regulation of mRNA Stability
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RNA masking and Polyadenylation

• Factors bind to stored mRNA and prevent
  translation
• smaug protein binds nanos mRNA
• mRNAs not polyadenylated
• deadenylated transcripts stable in oocyte
• Adenylation of transcript allows translation

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Antisense RNA Regulates Translation
Lin-4 RNA is complementary to several regions of
lin-14 3 UTR Formation of dsRNA prevents
translation of lin-14