transcription

• RNA pol 2 has a c terminal domain [CTD] .
• TF11H phosphorylates the CTD of RNA POL 2 .
• CTD phosphorylation creates anchor sites for proteins involved in 5 end capping , 3 end polyadenylation , splicing .
• Regulatory elements are short DNA sequences .
• Regulatory elements are different from one gene to another .
• Regulatory elements are very often palindromic .
• Transcriptional regulatory factors / activators are proteins that bind to specific sequences of DNA [regulatory elements] and control the transcription of genes.
• Activators have 3 domains :

  1. activation domain
  2. DNA binding domain
  3. dimerisation domain
• Dimer binding explains the palindromic nature of the regulatory element .
• DNA binding domain determines which regulatory element the activator will bind to and transcribe which gene .
• Activity of an activator can be controlled by signals :

  • presence of cytokines , growth factors
  • phosphorylation by a kinase
  • binding of a ligand
• Activators bind to major groove of DNA .
• In major grooves , there is asymmetrical contact points .

  Activators can distinguish this asymmetrical point .
• Activators work directly or indirectly via co activators to activate transcription .
• Co activators do not directly bind to DNA .
• Activators and co activators facilitate transcription by 2 mechanisms :

  1. By making DNA more accessible
  2. By recruiting the transcription machinery
• Making DNA more accessible :

  • enzymes acetylate N terminal of histones .
  • enzymes use energy to move nucleosomes.
• DNA b/w the regulatory sequence and promoter region must bend to allow the transcription machinery to interact with the activator .
• One activator controls many genes .
• Many regulatory elements are grouped together to form an enhancer or amplifier .