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TRANSCRIPTION :pen: (REGULATION :police_car: (RECRUIT RNA POLYMERASE…

- - - - 2 functional domains
        
        DNA binding domain - sequence specificity
        
        H-bond interaction between DNA bases and protein hydrophilic residues
        
        most TFs bind to at least 1 major groove
        
        classification of binding domain
        
        zinc finger
        
        leucine-zipper
        
        bHLH
        
        activation domain - activates transcription by protein - protein interaction
  - - - histone acetylation
        
        deacetylation - repression - condensed chromatin
        
        acetylation - activation - decondensation (loss of positive charge from lysine)
        
        protein with bromodomains bind to acetyl-lysine
        
        found in TFIID TAFs
        
        help recruit TFIID to acetylated histone
      - HISTONE METHYLATION
        
        no change in charge
        
        ex: HP1 recruit the histone methyle transferase - condense the chromatin
        
        proteins with chromodomains bind to methyl-lysine
        (found in protein activate of repress transcription)
    - - SWI/ SNF enzyme remodel chromotin
      - transcription activator mobilize nucleosome, expose the promoter
    - - CpG island promoter
        
        methylated by DNA mehtylases -> DNA condensation
        
        methyl CpG associates with histone condensation
  - - - reassemble of neucleosome
      - maintenance of histone methylation during DNA replication
      - maintenance of DNA methylation during DNA replication
  - - - LIGAND BINDING DOMAIN, activation domain, DNA binding domain
      - nuclear export/ import
      - homo-dimerization
        
        glucocoritcoid receptor
        
        bind to steroid in the cytosol
        
        move to the nucleus
        
        activate transcription
        
        estrogen receptor
      - hetero-dimerization
        
        thyroid hormone vitamin D, retinoic acid
        
        with ligand transcriptional activator
        
        without ligand transcription repression
- - - - phosphohydrolase - hydrolyze the 5' phosphate group
      - guanylyltransferase (capping enzyme) - add the guanosine monophosphate
      - methyltransferase - add a methyl group on the guanine base
  - - - CTD domain initiate cleavage
      - polymerase specificity - poly II CTD
      - sequence specificity- AAUAA
    - - bind to AAUAA - SF (polyadenylation specific factor)
      - CstF bind to G/U (cleavage stimulatory factor)
      - CF - leavage factor - cleave RNA
      - PAP - add adenosine to the moleucle
    - - slow polyadenylation
        
        stimulated by SF
        
        no template DNA
        
        PAP use ATP to add the poly A tail (first 20 adenosine)
      - fast polyadenylation
        
        stimulated by PABPII
        
        add up to 200 adenosine
  - - - OH group on exon 1 attack the 5' exon 2
      - exon 2 and lauriat structure + exon 1
      - OH group at branch point A attack the 3' of exon 1
    - - remove phosphodiester bond by some enzyme
      - degraded by exonuclease
    - - U2 hybridize with branch point A /
        U2AF recognize the 3' splice site
      - U1 snRNA hybridize with 5' splice site
    - - intron-exon 2
      - intron lariat
      - product: exon1 + exon 2
      - exon 1
      - substrate: exon 1 - intron - exon 2
    - - drosophila sex determination
        
        SxI protein recognize ISS - NOT splice at this loxation
        
        Tra protein recognizes an ESE - activate splicing and keep the middle exon
- - - - attach cargo in the cytosol
      - import into the nucleus
      - only unbind cargo when GTP binds
    - - cargo attached when GTP bind
      - will be released when GTP hydrolyzed (produce GDP)
    - - at the 5' cap: CBC -> eIF4E
      - at the poly A tail: PABPII to PABPI
  - - - protection from degredation
        
        AU
        
        -rich elements in the 3' UTR promote adenylation :question:
      - bind to actively transcribed mRNA
        
        bind to eIF4G and eIF4E @ 5' end forming looping structure
        
        slower the deandenylation of poly A tail
    - - deandenylate Poly A tail
      - DECAPPING ENZYME AT 5' END
      - EXOSOME 3'>>5'
      - XRN1 5'>>3'
      - remove looping structure
    - - DECAPPING ENZYME
      - XRN1 5'>>3'
    - - small RNA
        
        siRNA
        
        RISC complex cleave the mRNA
        
        perfect hybridization
        
        mRNA get degaded
        
        miRNA
        
        DROSHA process miRNA which has the looping structure
        
        RISC complex bind mRNA, imperfect hybridization - sit on mRNA - inhibit translation
        
        you get mRNA but not protein
        
        encoded in the genome
    - - exon surveillance
      - scan premature stop codon
- - - - sigma factor
        
        recruit RNA polymerase to bind to promoter
        
        bind to conserved promoter elements -10 to -35
      - core promoter
        
        dictate transcription start site + direction of transcription
        
        position RNA poly
      - DNA regulatory elements
        
        CAP
        
        cAMP
        
        activator
        
        lac operon
        
        repressor
    - - in response to changes in environment
      - GLOBAL TRANSCRIPTIONAL REGULATION
        
        transcriptional co-regulation of multiple genes
        different sigma factors recruit RNA polymerase to subset of gene promoter
        
        ex: response to heat shock, starvation
      - GENE-SPECIFIC TRANSCRIPTION REGULATION
        
        regulation of specific gene
        
        changes in food source
  - - - TATA BOX. initiatior
        
        highly transcribed genes
        
        defined start site
      - BRE
      - Inr
      - DPE
      - CpG islands
        
        lower transcription rate
        
        several start sites
      - dictate transcription state site and direction of transcription
    - - recruit TF
      - regulate transcription rate
    - - DNA elements that activate transcription
      - binding sites for TF
      - position and orientation independent, can be far away from transcription start site
      - promote tissue specific expression of genes
- - - - rRNA
        
        ribosome subunit
  - - - snRNA
        
        RNA splicing
      - mRNA
        
        encode protein
      - miRNA
        
        post-transcriptional control
    - - C-terminal domain CTD
        
        multiple copies of 7 aa repeat
        
        phosphorylation critical for transcription initiation and elongation
        
        critical mRNA processing
  - - - protein synthesis
      - aminoacylated tRNA -> tRNA-aa
    - - ribosome component
      - protein synthesis
      - 60S subunit (large)
    - - pre-mRNA splicing
      - spliceosome with U1, U2, U4, U5 snRNAs - Pol II transcript