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Eukaryotic Regulation - Coggle Diagram

- - - - aiding/preventing RNAP/Pol II recruitment
      - stimulating/inhibiting open RNAP complex
      - Facilitating promoter escape
  - - - More regulators
      - more signals
    - - Can also be influenced by GTF's including TFIID, and TBP
    - - Activators interact with GTF's, the mediator, and chromatin modifiers
    - - reminder: polycistronic = when one mRNA makes multiple gene products
    - - because of nucleus separating transcription and translation
    - - because default state is off
      - Activation occurs by activators
    - - leucine zippers
      - helix-loop-helix
      - zinc fingers
      - Proks use HTH (helix-turn-helix) motifs and act as dimers
- - - - Histone acetyltransferases (HAT)
        
        adds acetyl groups to histones to loosen chromatin
      - Histone deacetylases (HDAC)
        
        deacetylates histones to tighten chromatin
    - - recruits HDAC's
      - Prevents DNA binding protein/DNA interactions
      - Permanent gene silencing
      - 5% of cytosines in euks are methylated at CG repeats because 5-methyl-C deamination makes thymine and that is not good.
  - - - Nucleosome (includes histones)
        
        30nm filament
        
        Extended chromosome
        
        condensed chromosome
  - - - Heterochromatin - very tightly condensed, silenced
        
        10% of this kind of chromatin is telomeres, centromeres, and inactive sex chromosomes
        
        Methylation occurs at CpG dinucleotide repeats
        
        CpG = 5'—C—phosphate—G—3'
      - Euchromatin - less condensed but still condensed, not always active/silenced
        
        Histones are more likely to acetylated
- - - - euk activators do not interact with RNAP/Pol II directly, unlike proks
        
        That's why they need the activator domain
      - activator domain interacts with other proteins (known as coactivators)
        
        the mediator is an important coactivator recruited by epigenetic modifications
        
        coactivators - enhance transcription when bound to an activator-enhancer complex
        
        coactivators do NOT bond directly with DNA and usually don't directly interact with Pol II
        
        Exception: TFIID because only TBP subunit binds DNA
      - Regulates initiation by...
        
        recruiting HDAC's
        
        mediator interaction
        
        GTF/GTF-associated factor interaction
      - Usually more than one activator is required in euks
      - enhancers make activation specific
    - - Homeodomain - interacts with major and minor groves, a type of HTH, can dimerize
      - usually bind as a homodimer or a heterodimer
      - Zinc Fingers - often coordinated by two cysteine residues and two histidine residues
      - Leucine zippers - can be a homo or hetero dimer
      - helix-loop-helix domains - different from HTH
    - - Chromatin Modification
        
        nucleosome remodeling complex opens regulatory regions
        
        HAT's can also help with loosening of chromatin
      - Recruitment of Regulatory Proteins
        
        GTF's - usually TFIID or TFIIB
        
        Mediator complex
    - - promoter and regulatory regions are too far apart
      - different genes need different regulation
      - ensures specificity
  - - - May be as far away as 10,000+ bp up/downstream of core promoter
        
        core promoter - a group of DNA sequences in eukaryotes that common to promoters used by Pol II, has two required components and two optional components, recruits RNAP, +1 site
        
        Required
        
        TATA box
        
        Inr - initiator sequence
        
        Optional
        
        BRE - the TFIIB recognition element
        
        DPE - downstream promoter element
      - Direct timing of transcription
      - Direct transcriptional response to specific signals
      - UAS - upstream activator sequences
        
        usually found in lower euks, like yeast
        
        within 200bp of a gene
  - - - The platform for GTF assembly is made of the TBP subunit of TFIID
        
        TFIID bends DNA
- - - - modify nucleosome position or chromatin
      - blocks interactions between activators, coactivators, and RNAP
      - promotes histone/DNA modifications - may have HDAC activity
- - - - enhancer elements (UAS) are upstream of the promoter
  - - - an activator
        
        DNA binding domain = zinc finger
      - Binds to 17bp enhancer motif (UAS) as a dimer
        
        One or more of these per Gal4p-regulated gene
      - Interacts with...
        
        The mediator
        
        TBP/TFIID
        
        SAGA
        
        a histone acetylating complex (HAT)
        
        SWI/SNF nucleosome remodeling complex
    - - blocks Gal4p activation from interacting with TFIID/SWI/SNF/SAGA/The mediator
      - inhibits Gal4p
      - Prevents Pol II initiation complex
    - - Ligand sensor
      - Binds galactose (the effector)
      - turns Gal80p into a coactivator
  - - - Inhibition
        
        galactose is also low
        
        Gal4p bound to UAS sites
        
        Gal4p is bound by Gal80p
        
        No transcription due to prevented Gal4p/TFIID interaction
      - Activation
        
        Gal3p + ATP + glucose bind to Gal80p
        
        Gal80p becomes a coactivator
        
        Gal4p promotes transcription
    - - Inhibition
        
        Characters
        
        Mig1
        
        DNA binding protein = zinc finger
        
        a repressor protein
        
        binding site is upstream of GAL1 start site
        
        Tup1
        
        a corepressor
        
        binds Mig1
        
        Does NOT bind DNA directly
        
        recruits an HDAC
        
        represses chromatin
        
        Mechanism
        
        Absence of glucose
        
        Mig1 phosphorylated
        
        Mig1 can't enter nucleus therefore no repression
        
        Presence of glucose
        
        1) Mig1 dephosphorylated
        
        Mig1 enters nucleus and binds Mig1 binding site near Gal promoter
        
        2) Mig1 recruits Tup1
        
        3) Tup1 recruits HDAC's
        
        4) Repression
- - - - heterochromatin - condensed, generally inactive
      - euchromatin - transcriptionally active regions
    - - telomeres
      - centromeres
      - ribosomal DNA repeats (only half should be transcribed)
    - - direct methylation
        
        can promote HDAC recruitment
      - chromatin condensing
        
        usually deacetylation of histones by HDAC's
  - - - Typically at position 5 of cytosine
        
        source of 5-methyl cytosine damage
      - Directs heterochromatin formation by
        
        blocking DNA binding proteins (activators)
        
        recruiting HDAC's
    - - How it works (Steps)
        
        1) upon replication, new DNA is not methylated (hemimethylated state)
        
        3) HDAC's are recruited to methylated DNA to promote silencing
        
        2) Maintenance methylases are recruited to hemimethylated DNA to methylate
  - - - a growth-promoting hormone
      - inherited from dad
      - requires an enhancer for expression
      - Activation by methylation of insulator DNA (which prevents CTCF binding)
        
        paternal
      - Repression by the CTCF-bound-insulator
        
        maternal