regulation by xiaoyounan


									Gene Regulation
Thinking about Gene Regulation
 Humans begin life from a single cell,
  therefore all the genetic information needed
  to create a human is in our genome
 Embryonic cells undergo differentiation to
  produce specific cell types such as muscle,
  nerve, and blood cells
 Different cell types are the consequence of
  differential gene expression
    Thinking about Gene Regulation
 A typical differentiated mammalian cell
  makes about 10,000 proteins from
  approximately 35,000 genes
 Most of these are housekeeping proteins
  needed to maintain all cell types
 Certain proteins can only be detected in
  specific cell types
 How is gene expression regulated?
Regulation of Gene Expression

 Transcriptional control
 RNA processing control
 Translation control
 Protein activity control
Regulation of Gene Expression
                     Gene Organization
5’                                                           3’
        Promoter       Gene 1       Gene 2     Gene 3
3’                                                           5’

5’                                                            3’
        Promoter    Exon 1 Intron 1 Exon 2 Intron 2 Exon 3
3’                                                            5’
    Transcriptional Control
 Genes have regulatory DNA sequences
  upstream from the initiate site where
  transcription begins
 The promoter is the RNA polymerase
  binding site
 Gene regulatory proteins bind to regulatory
  DNA sequences and can either prevent or
  enhance RNA polymerase binding
Gene Regulatory Proteins Bind to DNA
DNA-binding motifs in proteins

  In the homeodomain,
  three alpha helices
  interact with the DNA.
DNA-binding motifs

  The zinc-finger motif is
  composed of an alpha
  helix and a beta sheet.

  Each zinc-finger is held
  together by a molecule
  of zinc
DNA-binding motifs

  In the leucine zipper
  motif, two alpha helices
  interact with the DNA.

  The two alpha helices
  are from different
Repressor Proteins

 Repressor proteins bind to an operator site
  within the promoter.
 Binding of a repressor prevents binding of
  RNA polymerase
 The repressor is an allosteric protein that
  can be activated by binding to a small
Regulation of tryptophan synthesis
Activator Proteins

 Activator proteins bind to DNA sequences
  and then interact with RNA polymerase to
  enhance its binding
 Activator proteins can be allosteric and bind
  to small molecules before they can bind to
Activator Proteins
Regulation of Eukaryotic Gene Expression

    General transcription factors are needed
     to initiate transcription
    Regulatory sequences: thousands of
     nucleotides from the promoter can influence
Highly methylated regions of DNA
correspond to inactive genes.
     promoter region                          coding region

enhancer TATA                      exon 1 intron 1 exon 2 term seq

         transcription factors
 factors  TBP
 enhancer TATA            Pol II   exon 1 intron 1 exon 2 term seq

         transcription factors
  factors  TBP
 enhancer TATA                                       exon 2 term seq
                                    exon 1 intron 1 II

      Regulation of Gene Expression by Upstream Elements

Operon (Lac, Trp):several genes controlled by single regulator
             operator-sequence to which repressor protein binds
             repressor-when bound inhibits transcription
             regulator gene-codes for repressor

Each gene with its own promoter region

Binding sites for basal transcription factors as well as sequence
specific binding proteins that activate or inhibit transcription

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