1. DNA Methylation:
  2. Histone Acetylation
  3. Homeotic Genes: master genes that control the pattern of body formation during early embryonic development
  • Ex: in flies genes control formation of body structures like body segments and antenna
    • Mutant homeotic genes produce body parts in wrong places
  • Homeobox is a specific nucleotide sequence that codes for protein
  • Hox genes contain homeobox and direct development of specific body part
    • Products of genes act as transcription factors
    • Appear in clusters and order on DNA controls order of expression and timing of body part development
  1. X inactivation:
  2. Transcription Initiation:
  3. Coactivators & Mediators: additional proteins that contribute to the binding of transcription complex components
  4. RNA processing/Alternative Splicing:
  5. RNA interference (RNAi): gene silencing caused by short noncoding RNA that bind to complementary sequences of mRNAs & block expression
  • Short Interfering RNAs (siRNAs): short double-stranded RNA, one strand is degraded → allows remaining strand to complement and inactivate a sequence of mRNA
  • Long noncoding RNA: some condense chromosome
  • PiRNA: reestablishes methylation patterns during gamete formation and block expression of some transposons → induce the formation of heterochromatin → block transcription
  • Dicer: Enzyme that trims small double-stranded RNAs into molecules that can block translation.                                         
  • MicroRNAs (miRNAs): Functions in RNA silencing and post-transcriptional regulation of gene expression.
    • Degrades mRNA if bases are completely complementary, If the match is less than complete, then translation is blocked
  1. MRNA degradation: occurs bcuz of RNAi and bcuz mRNA are unstable molecules
  • Poly-A-Tail and 5’ cap maintain mRNA stability but degradation slowly occurs as mRNA ages & degrading enzymes target tail and cap + untranslated UTR regions
  • Amount of protein made depends on rate of mRNA degradation
  1. Protein Degradation: final stage of proteins; as proteins age, they lose functionality as 3D shape changes → nonfunctional proteins marked for destruction with protein ubiquitin
  2. Protein Processing: protein chemical modification can activate/inactivate protein by adding/removing phosphate
  3. Translation Initiation: translation can be blocked by regulatory proteins that bind to untranslated sequence (UTR) at 5’ or 3’ end → prevents ribosomal attachment

Epigenetic (above the genes) Changes

  • Inheritance of traits transmitted by mechanisms not directly involving the nucleotide sequence
  • Do not alter DNA sequence,
  • Can affect gene expression through reversible modifications such as…
    • Histone acetylation, DNA methylation, genomic imprinting, X-inactivation

Regulation of Chromatin Structures

  • Histone modification: change in the organization of histone proteins with DNA.                                 
  • Access to DNA for transcription can be affected by..
  • Acetylation: enzymes add acetyl to histones → histones loosen grip on DNA → DNA uncoils → activated transcription
  • Methylation: enzymes attach methyl groups (-CH3) to histone proteins → histones tighten grip on DNA → preventing DNA from uncoiling and being expressed → repressed transcription
    • Protects against restriction fragments; DNA methylation inactivates genes (long-term)

Regulation of Transcription Initiation

  • After chromatin modification, transcription is next point of regulation
  • Transcription Initiation Complex: group of proteins associated with RNA pol II and inhibit/promote activity → make region of DNA more/less able to bind to transcription machinery
    • Proteins assemble on promoter sequence upstream (towards 5’ end) & adjacent to gene to be transcribed
    • Gene expression can be inhibited or activated by binding of repressors or activators to enhancers
  • General transcription factors: proteins required by all transcription events to initiate transcription
    • Some target the TATA box sequence associated with promoter
  • Specific transcription factors: other proteins associated with regulating specific transcription activities–specific to cell type, genes, or timing of transcription.
    • 2 kinds which bind to enhancers
      • Activators
      • Repressors: stop transcription & translation
    • Control Elements: segments of noncoding DNA that serve as binding sites for protein transcription factors to regulate transcription
      • DNA sequences located near (proximal) or far (distal) from the promoter, upstream
    • Enhancers: Distal control elements grouped together
    • Particular combination of control elements in an enhancer associated with a gene
      • Diff combination → diff regulation of transcription

Transcription Factors


  • Usually have DNA binding domains and binding domains for other transcription factors

Transcription factors as repressors:

  1. Bind to enhancers and block activators
  2. Silencing: bind to chromatin structure and remove acetyl

The Steps of Regulation of Transcription & Transcription Initiation Complex

  1. Enhancers bind to activator                                                                                                                           
  2. Since enhancer can be far from gene, a DNA-bending protein enables activators to bind to mediator proteins and general transcription factors at the promoter
  3. A transcription initiation complex is formed → initiate transcription