Eukaryote Gene Regulation

• Eukaryote gene regulation


  The expression of eukaryotic genes is different from prokaryotes
• Any human cell probably only expresses about 20% of its genes at a time, and this proportion is even lower in highly specialized cells (ex.: muscle cells, neurons)
• Multicellular organisms must activate or deactivate their genes according to

  • External stimuli
  • Internal stimuli
  • Regulate genes according to the type of cell (liver, skin, etc.)
• Chromatin


  A complex of DNA and protein found in eukaryotic cells
• Chromatin


  • The primary protein components are histones, which bind to DNA and wrap around the histone
  • The primary function is to pack DNA into more compact structures

  
• To be readable, DNA needs to be accessible to the RNA Polymerase II


  Chromatin structure needs to be modified

  
• Histone acetylation


  Leads to the loosening of the structure of chromatin
• Loose chromatin structure


  Permits access of the RNA polymerase to the DNA and the initiation of transcription

  
• Histone methylation


  Is in general associated with transcriptional repression
• Histone methylation


  • It depends on which amino acids in the histones are methylated, and how many methyl groups are attached
  • Methylation of some lysine and arginine residues of histones results in transcriptional activation
• ATP-dependent chromatin remodeling factors

  • Function as molecular motors that use energy from ATP hydrolysis to alter the relationships between histones and DNA
  • Make DNA more accessible to regulatory proteins that in turn affect gene expression

  
• DNA methylation


  Addition of methyl groups to certain bases in DNA is associated with reduced transcription in certain species (deactivates genes)

  
• Epigenetic inheritance


  • The inheritance of traits transmitted by mechanisms not directly involving the nucleotide sequence
  • DNA methylation and histone modification changes the way genes are expressed but not the DNA sequence
• For example, rice plants exposed to drought had offspring with increased tolerance to drought due to induce DNA methylation patterns
• Epigenetic


  An alteration that must persist in the absence of the initiating stimulus, and be inherited through cell division
• Structure of a gene typical of Eukaryotes

  • Promoter
  • Transcription factors
  • RNA polymerase II
  • m-RNA
• Transcription factors


  Proteins that help eukaryotic RNA polymerase II initiate transcription
• Types of transcription factors

  • General transcription factors
  • Specific transcription factors
• General transcription factors


  Are necessary for the assembly of a transcription apparatus and recruitment of RNA polymerase II to a promoter to initiate transcription
• Specific transcription factors


  Increase the level of transcription in certain cell types or in response to signals
• RNA polymerase II


  Enzyme that transcribes DNA into mRNA
• Initiation of the transcription complex

  Recruitment of RNA polymerase II to a promoter to initiate transcription
• Promoter


  DNA sequence that initiates transcription of a particular gene
• Eukaryote gene regulation


  The control of gene expression in eukaryotic cells
• Regulation of transcription initiation


  Steps involved in starting the transcription of a gene
• General transcription factors


  • Are necessary for the assembly of a transcription apparatus and recruitment of RNA polymerase II to a promoter to initiate transcription
  • Do not increase the rate of transcription above the basal level
• The general transcription factors are proteins that bind to the DNA promoter
• Transcription factors


  Proteins that regulate the transcription of genes
• Activators


  • Act in a specific tissue or in a time dependent manner to stimulate higher levels of transcription than the basal level
• Activator protein domains


  • DNA-binding domain that recognize a specific sequence of DNA
  • Activation domain that interacts with the transcription apparatus
• Enhancer and specific transcription factors

  1. Linked activators facilitate a sequence of protein-protein interactions leading to the enhanced transcription of a given gene

  2. Bends DNA so that activator is on top of where promoter is
• Coactivator or mediator proteins


  • Interact with activators and the transcription apparatus to enhance transcription
• Control of the activation of genes

  1. A combination of control elements can only activate transcription when the appropriate activator proteins are present

  2. Each enhancer is composed of approximately 10 control elements
• Virtually all genes that are transcribed by RNA polymerase II need the same suite of general factors to assemble an initiation complex
• The ultimate level of transcription depends on the presence of activators, coactivators, and mediator proteins
• Eukaryote gene regulation


  The control of gene expression in eukaryotic cells at multiple levels including chromatin modification, transcription, RNA maturation, translation, and protein degradation
• Pre-mRNA alternative splicing


  Different mRNA molecules are produced from the same primary transcript
• Human have about 21,000 genes, but can make 100,000 proteins
• Degradation of the mRNA

  The lifespan of eukaryotic mRNA is higher (half life of 10 hrs) than prokaryotic mRNA (half life of 3 mins)
• The nucleotide sequences that influence the lifespan of mRNA in eukaryotes reside in the untranslated region (UTR) at the 3' end of the molecule