Updated: 11/1/2017

Transcription Regulation

0%
Topic
Review Topic
0
0
N/A
N/A
Questions
2 2
0
0
0%
0%
Evidence
1 1
0
0
0%
0%
Videos
1 1
Overview
  •  Function
    • can turn transcription on/off
    • can ↑ or ↓ rate of transcription
    • can act in cis or trans
      • cis = regulation near gene locus
        • DNA binding sequence
        • a mutated cis regulatory element can result in gene that is constitutively on or off
      • trans = regulation from gene locus
        • transcription factor protein
        • because it acts at a distance a good allelic copy can compensate for a mutated copy
  • Mechanisms of control 
    • modify RNAp binding stability
      • transcription factors
        • function
          • modify basal transcription levels
          • two types
            • general
              • must bind to DNA and RNAp to begin baseline transcription of most every gene
              • e.g. TFIID binds TATA box and RNAp II
            • specific
              • acts through enhancers and silencers
              • can regulate specific gene responses
        • structure
          • DNA binding domain
            • can be zinc fingers, helix-turn-helix, helix-loop-helix, or leucine zippers
          • regulatory element binding domain
            • e.g. binds hormone, ion, other transcription factors, etc.
    • modify RNAp accessibility to DNA
      • histone modifiers
        • histone acetylases (HATs) open DNA and ↑ transcription 
        • histone deacetylase (HDACs) close DNA and ↓ transcription
        • see Chromatin Structure topic
      • imprinting
        • methylation effectively shuts a gene off
          • often irreversible
        • some genes methylate a gene locus on paternal or maternal chromosome
          • allows only one allele to be active
          • e.g. Prader-Willi/Angelman syndrome
        • see Epigenetics topic
      • inactivation of a chromosome
        • condensation of # of X chromosomes - 1 to form Barr bodies
          • e.g. Turner's Syndrome (XO) the patient would have no Barr bodies as they only have 1 X chromosome
      • increase number of gene copies
        • more sites for RNAp to bind
        • common in oncogenes
  • Embryonic gene regulation
    • sonic hedgehog (SHH) gene
      • mutations causes holoprosencephaly (HPE)
        • failure of midline brain to separate into right and left
    • homeobox (HOX) genes
      • control proper timing of gene activation
    • paired box (PAX) genes
      • mutations cause Klein-Waardenburg syndrome
        • presentation
          • neural crest abnormalities
            • deafness
            • variation in pigmentation
              • forelock of white hair
              • patches of different colored skin
            • dystopia canthorum
              • broad nasal root
  • Examples of gene regulation
    • peroxisome proliferator-activated receptors (PPARs)
      • controls fat metabolism
        • turned on by endogenous ligands
          • fatty acids, prostaglandins
        • also turned on by exogenous ligands
          • fibrates, thiazolidinediones
      • bind PPRE region in DNA
      • clinical importance
        • fibrates given to hyperlipidemic patients to ↑ transcription of lipoprotein lipase
          • also used in treatment for Zellweger syndrome

 

 

Please rate topic.

Average 4.8 of 4 Ratings

Questions (2)
Question locked
Sorry, this question is for
PEAK Premium Subscribers only
Upgrade to PEAK
Question locked
Sorry, this question is for
PEAK Premium Subscribers only
Upgrade to PEAK
Evidence (1)
VIDEOS (1)
Topic COMMENTS (29)
Private Note