Differential Gene Expression

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					Differential Gene Expression

  Turning Genes on or keeping them off?
   Differential Gene Regulation
• Transcriptional regulation
• Post-transcriptional regulation
• Translational regulation
• Post-translational regulation
    Differential Gene Expression
• Transcriptional • Transcription factor
• Post-transcriptional     binding
• Translational          • Transcription factor
• Post-translational       interactions
                         • Methylation
                         • Nucleosome/chromatin
    Differential Gene Expression
• Transcriptional      • Splicing
• Post-transcriptional • Polyadenylation
• Translational        • Stability
• Post-translational
    Differential Gene Expression
• Transcriptional        • Masking
• Post-transcriptional   • Antisense RNA
• Translational
• Post-translational
    Differential Gene Expression
• Transcriptional        • Glycosylation
• Post-transcriptional   • Acylation
• Translational
                         • Proteolytic processing
• Post-translational
   Differential Gene Regulation
• Hierarchies of transcriptional regulatory
  – Transcription Factors
• Regulators of regulators
Transcriptional Activation
 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
             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
        Transcription Factors

• Gene Specific Txn Factors
  – Classified by DNA binding domains & mechanism of
    transcriptional activation
Transcription Factor Flavors
       Family               Representative
          Hox                Hoxa-1, Antp, eve, en
          POU             Pit-1,Unc-86, Oct-2, Brn-5
          LIM                    Lim-1, Isl-1
       Paired Box               Pax-1,2,6, Prd
 Forkhead/Winged Helix          Fkh, HNF-3
 Basic-helix-loop-helix      MyoD, Ac, da, emc

 Basic leucine-zipper         AP1, Myc, C/EBP
        standard           WT-1, Krox-20, Kr, hb
    steroid receptors       GR, ER, RAR, kni

          Sox                  Sry, SoxD, Sox2
      MADS box                 MEF-1, MCM-1
Take A Look

  Website 5.4
Physical Arrangement of
 Regulatory Elements
Cell-Type Specific Transcription
• Tissue specificity
• Promoter
• Enhancer
• Tissue specific txn factor and cognizant
  DNA element (site)
Epigenetic Gene Regulation
Differential Gene Expression Via
 Posttranscriptional Regulation
       Alternative or Differential Splicing
         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
              Differential Splicing
Sex Determination in Drosophila Regulated by Differential Splicing
Differential Splicing & Sex

       Girls              Boys
3’ UTR Mediates Stability or

                U-Rich 3’UTR mediates
                degradation of
Regulation of mRNA Stability
             RNA masking and
• Factors bind to stored mRNA and prevent
  – smaug protein binds nanos mRNA
• mRNAs not polyadenylated
  – deadenylated transcripts stable in oocyte
• Adenylation of transcript allows translation
Antisense RNA Regulates
Lin-4 RNA is complementary to
several regions of lin-14 3’ UTR

Formation of dsRNA prevents
translation of lin-14

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